Review



cx 5461  (MedChemExpress)


Bioz Verified Symbol MedChemExpress is a verified supplier
Bioz Manufacturer Symbol MedChemExpress manufactures this product  
  • Logo
  • About
  • News
  • Press Release
  • Team
  • Advisors
  • Partners
  • Contact
  • Bioz Stars
  • Bioz vStars
  • 94

    Structured Review

    MedChemExpress cx 5461
    Effects of pyrimidine biosynthesis-driven pre-rRNA synthesis on lactate-induced ECM production. a , b Effects of 24 h exposure to AR-C155858 (2 µM, a) or BRQ (0.1 µM, b) on puromycin incorporation in LX-2 cells cultured in the presence or absence of lactate (10 mM). c Immunofluorescence staining for puromycin (1 µg/mL) in LX-2 cells showing the effects of BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). d Pull-down assay showing the effects of BRQ (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in the presence or absence of lactate (10 mM, 24 h). e UTP levels in LX-2 cells treated with BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right) ( n = 3). f Effects of BRQ or uridine on COL1A1 and FN1 protein levels in LX-2 cells. LX-2 cells were treated with BRQ (0.1 µM) or uridine (5, 20, or 50 µM) in the absence or presence of lactate (10 mM) for 24 h (left panel). LX-2 cells cultured in Huh7-derived CM were treated with BRQ (0.1 µM) in the absence or presence of uridine (50 µM) for 24 h (right panel). g Immunofluorescence staining of Y10B in LX-2 cells showing the effects of BRQ (0.1 µM) or uridine (50 µM) exposure for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right). h Relative expression of 5′ ETS in LX-2 cells treated with BRQ (0.1 µM) or uridine (50 µM) for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right) ( n = 3). i Effects <t>of</t> <t>CX-5461</t> (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). j Effects of MCT1 - or DHODH -targeting siRNA on COL1A1 (red) and FN1 (green) immunofluorescence staining in LX-2 cells co-cultured with Huh7 cells and treated with uridine (50 µM, 24 h). k Schematic model illustrating lactate-driven mTORC1 activation and its role in ECM production via the pre-rRNA synthesis pathway in HSCs. Created with BioRender.com, agreement number: MP29JVSCPU. Scale bar: 75 µm. Data are presented as the mean ± SEM from at least three independent experiments. n.s., Not significant; ** p < 0.01; *** p < 0.001. BRQ, Brequinar
    Cx 5461, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 94/100, based on 40 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/cx 5461/product/MedChemExpress
    Average 94 stars, based on 40 article reviews
    cx 5461 - by Bioz Stars, 2026-06
    94/100 stars

    Images

    1) Product Images from "Lactate-driven pyrimidine synthesis promotes ferroptosis resistance in hepatocellular carcinoma"

    Article Title: Lactate-driven pyrimidine synthesis promotes ferroptosis resistance in hepatocellular carcinoma

    Journal: Molecular Biomedicine

    doi: 10.1186/s43556-026-00450-3

    Effects of pyrimidine biosynthesis-driven pre-rRNA synthesis on lactate-induced ECM production. a , b Effects of 24 h exposure to AR-C155858 (2 µM, a) or BRQ (0.1 µM, b) on puromycin incorporation in LX-2 cells cultured in the presence or absence of lactate (10 mM). c Immunofluorescence staining for puromycin (1 µg/mL) in LX-2 cells showing the effects of BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). d Pull-down assay showing the effects of BRQ (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in the presence or absence of lactate (10 mM, 24 h). e UTP levels in LX-2 cells treated with BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right) ( n = 3). f Effects of BRQ or uridine on COL1A1 and FN1 protein levels in LX-2 cells. LX-2 cells were treated with BRQ (0.1 µM) or uridine (5, 20, or 50 µM) in the absence or presence of lactate (10 mM) for 24 h (left panel). LX-2 cells cultured in Huh7-derived CM were treated with BRQ (0.1 µM) in the absence or presence of uridine (50 µM) for 24 h (right panel). g Immunofluorescence staining of Y10B in LX-2 cells showing the effects of BRQ (0.1 µM) or uridine (50 µM) exposure for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right). h Relative expression of 5′ ETS in LX-2 cells treated with BRQ (0.1 µM) or uridine (50 µM) for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right) ( n = 3). i Effects of CX-5461 (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). j Effects of MCT1 - or DHODH -targeting siRNA on COL1A1 (red) and FN1 (green) immunofluorescence staining in LX-2 cells co-cultured with Huh7 cells and treated with uridine (50 µM, 24 h). k Schematic model illustrating lactate-driven mTORC1 activation and its role in ECM production via the pre-rRNA synthesis pathway in HSCs. Created with BioRender.com, agreement number: MP29JVSCPU. Scale bar: 75 µm. Data are presented as the mean ± SEM from at least three independent experiments. n.s., Not significant; ** p < 0.01; *** p < 0.001. BRQ, Brequinar
    Figure Legend Snippet: Effects of pyrimidine biosynthesis-driven pre-rRNA synthesis on lactate-induced ECM production. a , b Effects of 24 h exposure to AR-C155858 (2 µM, a) or BRQ (0.1 µM, b) on puromycin incorporation in LX-2 cells cultured in the presence or absence of lactate (10 mM). c Immunofluorescence staining for puromycin (1 µg/mL) in LX-2 cells showing the effects of BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). d Pull-down assay showing the effects of BRQ (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in the presence or absence of lactate (10 mM, 24 h). e UTP levels in LX-2 cells treated with BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right) ( n = 3). f Effects of BRQ or uridine on COL1A1 and FN1 protein levels in LX-2 cells. LX-2 cells were treated with BRQ (0.1 µM) or uridine (5, 20, or 50 µM) in the absence or presence of lactate (10 mM) for 24 h (left panel). LX-2 cells cultured in Huh7-derived CM were treated with BRQ (0.1 µM) in the absence or presence of uridine (50 µM) for 24 h (right panel). g Immunofluorescence staining of Y10B in LX-2 cells showing the effects of BRQ (0.1 µM) or uridine (50 µM) exposure for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right). h Relative expression of 5′ ETS in LX-2 cells treated with BRQ (0.1 µM) or uridine (50 µM) for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right) ( n = 3). i Effects of CX-5461 (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). j Effects of MCT1 - or DHODH -targeting siRNA on COL1A1 (red) and FN1 (green) immunofluorescence staining in LX-2 cells co-cultured with Huh7 cells and treated with uridine (50 µM, 24 h). k Schematic model illustrating lactate-driven mTORC1 activation and its role in ECM production via the pre-rRNA synthesis pathway in HSCs. Created with BioRender.com, agreement number: MP29JVSCPU. Scale bar: 75 µm. Data are presented as the mean ± SEM from at least three independent experiments. n.s., Not significant; ** p < 0.01; *** p < 0.001. BRQ, Brequinar

    Techniques Used: Cell Culture, Immunofluorescence, Staining, Pull Down Assay, Derivative Assay, Expressing, Activation Assay



    Similar Products

    94
    MedChemExpress cx 5461
    Effects of pyrimidine biosynthesis-driven pre-rRNA synthesis on lactate-induced ECM production. a , b Effects of 24 h exposure to AR-C155858 (2 µM, a) or BRQ (0.1 µM, b) on puromycin incorporation in LX-2 cells cultured in the presence or absence of lactate (10 mM). c Immunofluorescence staining for puromycin (1 µg/mL) in LX-2 cells showing the effects of BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). d Pull-down assay showing the effects of BRQ (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in the presence or absence of lactate (10 mM, 24 h). e UTP levels in LX-2 cells treated with BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right) ( n = 3). f Effects of BRQ or uridine on COL1A1 and FN1 protein levels in LX-2 cells. LX-2 cells were treated with BRQ (0.1 µM) or uridine (5, 20, or 50 µM) in the absence or presence of lactate (10 mM) for 24 h (left panel). LX-2 cells cultured in Huh7-derived CM were treated with BRQ (0.1 µM) in the absence or presence of uridine (50 µM) for 24 h (right panel). g Immunofluorescence staining of Y10B in LX-2 cells showing the effects of BRQ (0.1 µM) or uridine (50 µM) exposure for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right). h Relative expression of 5′ ETS in LX-2 cells treated with BRQ (0.1 µM) or uridine (50 µM) for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right) ( n = 3). i Effects <t>of</t> <t>CX-5461</t> (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). j Effects of MCT1 - or DHODH -targeting siRNA on COL1A1 (red) and FN1 (green) immunofluorescence staining in LX-2 cells co-cultured with Huh7 cells and treated with uridine (50 µM, 24 h). k Schematic model illustrating lactate-driven mTORC1 activation and its role in ECM production via the pre-rRNA synthesis pathway in HSCs. Created with BioRender.com, agreement number: MP29JVSCPU. Scale bar: 75 µm. Data are presented as the mean ± SEM from at least three independent experiments. n.s., Not significant; ** p < 0.01; *** p < 0.001. BRQ, Brequinar
    Cx 5461, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/cx 5461/product/MedChemExpress
    Average 94 stars, based on 1 article reviews
    cx 5461 - by Bioz Stars, 2026-06
    94/100 stars
      Buy from Supplier

    95
    MedChemExpress cells
    Effects of pyrimidine biosynthesis-driven pre-rRNA synthesis on lactate-induced ECM production. a , b Effects of 24 h exposure to AR-C155858 (2 µM, a) or BRQ (0.1 µM, b) on puromycin incorporation in LX-2 cells cultured in the presence or absence of lactate (10 mM). c Immunofluorescence staining for puromycin (1 µg/mL) in LX-2 cells showing the effects of BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). d Pull-down assay showing the effects of BRQ (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in the presence or absence of lactate (10 mM, 24 h). e UTP levels in LX-2 cells treated with BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right) ( n = 3). f Effects of BRQ or uridine on COL1A1 and FN1 protein levels in LX-2 cells. LX-2 cells were treated with BRQ (0.1 µM) or uridine (5, 20, or 50 µM) in the absence or presence of lactate (10 mM) for 24 h (left panel). LX-2 cells cultured in Huh7-derived CM were treated with BRQ (0.1 µM) in the absence or presence of uridine (50 µM) for 24 h (right panel). g Immunofluorescence staining of Y10B in LX-2 cells showing the effects of BRQ (0.1 µM) or uridine (50 µM) exposure for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right). h Relative expression of 5′ ETS in LX-2 cells treated with BRQ (0.1 µM) or uridine (50 µM) for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right) ( n = 3). i Effects <t>of</t> <t>CX-5461</t> (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). j Effects of MCT1 - or DHODH -targeting siRNA on COL1A1 (red) and FN1 (green) immunofluorescence staining in LX-2 cells co-cultured with Huh7 cells and treated with uridine (50 µM, 24 h). k Schematic model illustrating lactate-driven mTORC1 activation and its role in ECM production via the pre-rRNA synthesis pathway in HSCs. Created with BioRender.com, agreement number: MP29JVSCPU. Scale bar: 75 µm. Data are presented as the mean ± SEM from at least three independent experiments. n.s., Not significant; ** p < 0.01; *** p < 0.001. BRQ, Brequinar
    Cells, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 95/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/cells/product/MedChemExpress
    Average 95 stars, based on 1 article reviews
    cells - by Bioz Stars, 2026-06
    95/100 stars
      Buy from Supplier

    95
    MedChemExpress cx5461
    Effects of pyrimidine biosynthesis-driven pre-rRNA synthesis on lactate-induced ECM production. a , b Effects of 24 h exposure to AR-C155858 (2 µM, a) or BRQ (0.1 µM, b) on puromycin incorporation in LX-2 cells cultured in the presence or absence of lactate (10 mM). c Immunofluorescence staining for puromycin (1 µg/mL) in LX-2 cells showing the effects of BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). d Pull-down assay showing the effects of BRQ (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in the presence or absence of lactate (10 mM, 24 h). e UTP levels in LX-2 cells treated with BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right) ( n = 3). f Effects of BRQ or uridine on COL1A1 and FN1 protein levels in LX-2 cells. LX-2 cells were treated with BRQ (0.1 µM) or uridine (5, 20, or 50 µM) in the absence or presence of lactate (10 mM) for 24 h (left panel). LX-2 cells cultured in Huh7-derived CM were treated with BRQ (0.1 µM) in the absence or presence of uridine (50 µM) for 24 h (right panel). g Immunofluorescence staining of Y10B in LX-2 cells showing the effects of BRQ (0.1 µM) or uridine (50 µM) exposure for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right). h Relative expression of 5′ ETS in LX-2 cells treated with BRQ (0.1 µM) or uridine (50 µM) for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right) ( n = 3). i Effects <t>of</t> <t>CX-5461</t> (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). j Effects of MCT1 - or DHODH -targeting siRNA on COL1A1 (red) and FN1 (green) immunofluorescence staining in LX-2 cells co-cultured with Huh7 cells and treated with uridine (50 µM, 24 h). k Schematic model illustrating lactate-driven mTORC1 activation and its role in ECM production via the pre-rRNA synthesis pathway in HSCs. Created with BioRender.com, agreement number: MP29JVSCPU. Scale bar: 75 µm. Data are presented as the mean ± SEM from at least three independent experiments. n.s., Not significant; ** p < 0.01; *** p < 0.001. BRQ, Brequinar
    Cx5461, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 95/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/cx5461/product/MedChemExpress
    Average 95 stars, based on 1 article reviews
    cx5461 - by Bioz Stars, 2026-06
    95/100 stars
      Buy from Supplier

    86
    Merck & Co rna polymerase i inhibitor cx 5461
    Effects of pyrimidine biosynthesis-driven pre-rRNA synthesis on lactate-induced ECM production. a , b Effects of 24 h exposure to AR-C155858 (2 µM, a) or BRQ (0.1 µM, b) on puromycin incorporation in LX-2 cells cultured in the presence or absence of lactate (10 mM). c Immunofluorescence staining for puromycin (1 µg/mL) in LX-2 cells showing the effects of BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). d Pull-down assay showing the effects of BRQ (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in the presence or absence of lactate (10 mM, 24 h). e UTP levels in LX-2 cells treated with BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right) ( n = 3). f Effects of BRQ or uridine on COL1A1 and FN1 protein levels in LX-2 cells. LX-2 cells were treated with BRQ (0.1 µM) or uridine (5, 20, or 50 µM) in the absence or presence of lactate (10 mM) for 24 h (left panel). LX-2 cells cultured in Huh7-derived CM were treated with BRQ (0.1 µM) in the absence or presence of uridine (50 µM) for 24 h (right panel). g Immunofluorescence staining of Y10B in LX-2 cells showing the effects of BRQ (0.1 µM) or uridine (50 µM) exposure for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right). h Relative expression of 5′ ETS in LX-2 cells treated with BRQ (0.1 µM) or uridine (50 µM) for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right) ( n = 3). i Effects <t>of</t> <t>CX-5461</t> (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). j Effects of MCT1 - or DHODH -targeting siRNA on COL1A1 (red) and FN1 (green) immunofluorescence staining in LX-2 cells co-cultured with Huh7 cells and treated with uridine (50 µM, 24 h). k Schematic model illustrating lactate-driven mTORC1 activation and its role in ECM production via the pre-rRNA synthesis pathway in HSCs. Created with BioRender.com, agreement number: MP29JVSCPU. Scale bar: 75 µm. Data are presented as the mean ± SEM from at least three independent experiments. n.s., Not significant; ** p < 0.01; *** p < 0.001. BRQ, Brequinar
    Rna Polymerase I Inhibitor Cx 5461, supplied by Merck & Co, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/rna polymerase i inhibitor cx 5461/product/Merck & Co
    Average 86 stars, based on 1 article reviews
    rna polymerase i inhibitor cx 5461 - by Bioz Stars, 2026-06
    86/100 stars
      Buy from Supplier

    86
    Molecular Dynamics Inc cx 5461
    Effects of pyrimidine biosynthesis-driven pre-rRNA synthesis on lactate-induced ECM production. a , b Effects of 24 h exposure to AR-C155858 (2 µM, a) or BRQ (0.1 µM, b) on puromycin incorporation in LX-2 cells cultured in the presence or absence of lactate (10 mM). c Immunofluorescence staining for puromycin (1 µg/mL) in LX-2 cells showing the effects of BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). d Pull-down assay showing the effects of BRQ (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in the presence or absence of lactate (10 mM, 24 h). e UTP levels in LX-2 cells treated with BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right) ( n = 3). f Effects of BRQ or uridine on COL1A1 and FN1 protein levels in LX-2 cells. LX-2 cells were treated with BRQ (0.1 µM) or uridine (5, 20, or 50 µM) in the absence or presence of lactate (10 mM) for 24 h (left panel). LX-2 cells cultured in Huh7-derived CM were treated with BRQ (0.1 µM) in the absence or presence of uridine (50 µM) for 24 h (right panel). g Immunofluorescence staining of Y10B in LX-2 cells showing the effects of BRQ (0.1 µM) or uridine (50 µM) exposure for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right). h Relative expression of 5′ ETS in LX-2 cells treated with BRQ (0.1 µM) or uridine (50 µM) for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right) ( n = 3). i Effects <t>of</t> <t>CX-5461</t> (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). j Effects of MCT1 - or DHODH -targeting siRNA on COL1A1 (red) and FN1 (green) immunofluorescence staining in LX-2 cells co-cultured with Huh7 cells and treated with uridine (50 µM, 24 h). k Schematic model illustrating lactate-driven mTORC1 activation and its role in ECM production via the pre-rRNA synthesis pathway in HSCs. Created with BioRender.com, agreement number: MP29JVSCPU. Scale bar: 75 µm. Data are presented as the mean ± SEM from at least three independent experiments. n.s., Not significant; ** p < 0.01; *** p < 0.001. BRQ, Brequinar
    Cx 5461, supplied by Molecular Dynamics Inc, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/cx 5461/product/Molecular Dynamics Inc
    Average 86 stars, based on 1 article reviews
    cx 5461 - by Bioz Stars, 2026-06
    86/100 stars
      Buy from Supplier

    Image Search Results


    Effects of pyrimidine biosynthesis-driven pre-rRNA synthesis on lactate-induced ECM production. a , b Effects of 24 h exposure to AR-C155858 (2 µM, a) or BRQ (0.1 µM, b) on puromycin incorporation in LX-2 cells cultured in the presence or absence of lactate (10 mM). c Immunofluorescence staining for puromycin (1 µg/mL) in LX-2 cells showing the effects of BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). d Pull-down assay showing the effects of BRQ (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in the presence or absence of lactate (10 mM, 24 h). e UTP levels in LX-2 cells treated with BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right) ( n = 3). f Effects of BRQ or uridine on COL1A1 and FN1 protein levels in LX-2 cells. LX-2 cells were treated with BRQ (0.1 µM) or uridine (5, 20, or 50 µM) in the absence or presence of lactate (10 mM) for 24 h (left panel). LX-2 cells cultured in Huh7-derived CM were treated with BRQ (0.1 µM) in the absence or presence of uridine (50 µM) for 24 h (right panel). g Immunofluorescence staining of Y10B in LX-2 cells showing the effects of BRQ (0.1 µM) or uridine (50 µM) exposure for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right). h Relative expression of 5′ ETS in LX-2 cells treated with BRQ (0.1 µM) or uridine (50 µM) for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right) ( n = 3). i Effects of CX-5461 (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). j Effects of MCT1 - or DHODH -targeting siRNA on COL1A1 (red) and FN1 (green) immunofluorescence staining in LX-2 cells co-cultured with Huh7 cells and treated with uridine (50 µM, 24 h). k Schematic model illustrating lactate-driven mTORC1 activation and its role in ECM production via the pre-rRNA synthesis pathway in HSCs. Created with BioRender.com, agreement number: MP29JVSCPU. Scale bar: 75 µm. Data are presented as the mean ± SEM from at least three independent experiments. n.s., Not significant; ** p < 0.01; *** p < 0.001. BRQ, Brequinar

    Journal: Molecular Biomedicine

    Article Title: Lactate-driven pyrimidine synthesis promotes ferroptosis resistance in hepatocellular carcinoma

    doi: 10.1186/s43556-026-00450-3

    Figure Lengend Snippet: Effects of pyrimidine biosynthesis-driven pre-rRNA synthesis on lactate-induced ECM production. a , b Effects of 24 h exposure to AR-C155858 (2 µM, a) or BRQ (0.1 µM, b) on puromycin incorporation in LX-2 cells cultured in the presence or absence of lactate (10 mM). c Immunofluorescence staining for puromycin (1 µg/mL) in LX-2 cells showing the effects of BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). d Pull-down assay showing the effects of BRQ (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in the presence or absence of lactate (10 mM, 24 h). e UTP levels in LX-2 cells treated with BRQ (0.1 µM, 24 h) in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right) ( n = 3). f Effects of BRQ or uridine on COL1A1 and FN1 protein levels in LX-2 cells. LX-2 cells were treated with BRQ (0.1 µM) or uridine (5, 20, or 50 µM) in the absence or presence of lactate (10 mM) for 24 h (left panel). LX-2 cells cultured in Huh7-derived CM were treated with BRQ (0.1 µM) in the absence or presence of uridine (50 µM) for 24 h (right panel). g Immunofluorescence staining of Y10B in LX-2 cells showing the effects of BRQ (0.1 µM) or uridine (50 µM) exposure for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right). h Relative expression of 5′ ETS in LX-2 cells treated with BRQ (0.1 µM) or uridine (50 µM) for 24 h in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, right) ( n = 3). i Effects of CX-5461 (0.1 µM, 24 h) on COL1A1 and FN1 protein levels in LX-2 cells cultured in CM from Huh7 cells (left) or in the presence or absence of lactate (10 mM, 24 h, right). j Effects of MCT1 - or DHODH -targeting siRNA on COL1A1 (red) and FN1 (green) immunofluorescence staining in LX-2 cells co-cultured with Huh7 cells and treated with uridine (50 µM, 24 h). k Schematic model illustrating lactate-driven mTORC1 activation and its role in ECM production via the pre-rRNA synthesis pathway in HSCs. Created with BioRender.com, agreement number: MP29JVSCPU. Scale bar: 75 µm. Data are presented as the mean ± SEM from at least three independent experiments. n.s., Not significant; ** p < 0.01; *** p < 0.001. BRQ, Brequinar

    Article Snippet: LX-2 cells were treated with CM, sodium L-lactate (10 mM; Sigma), AR–C 155858 (2 μM; MedChemExpress, Monmouth Junction, NJ, USA), rapamycin (20 nM; Sigma), PALA (150 μM; MedChemExpress), BRQ (0.1 μM; Selleckchem, Houston, TX, USA), uridine (5, 10, 50 μM; Sigma), cytidine (50 μM, Sigma), mitoQH 2 (0.1 μM; Cayman, Ann Arbor, MI, USA), and CX-5461 (0.1 μM; MedChemExpress) for 24 h. Huh7 and PLC/PRF/5 cells were treated with IKE (1 μM; Selleckchem) and sorafenib (10 μM; Selleckchem) for 6 h, and ferrostatin-1 (1 μM, Sigma), Z-VAD-FMK (20 μM; Selleckchem), necrostatin-1 (20 μM; MedChemExpress), and MGH-CP1 (2 μM, MedChemExpress) were applied for 24 h. For collagen and fibronectin stimulation, cells were serum-starved for 10 h and then treated with collagen I (30 μg/mL; Corning, NY, USA) or fibronectin (30 μg/mL; R&D Systems, MN, USA) for 24 h in the presence or absence of verteporfin (1 μM; MedChemExpress).

    Techniques: Cell Culture, Immunofluorescence, Staining, Pull Down Assay, Derivative Assay, Expressing, Activation Assay