Journal: Cell Death Discovery

Article Title: APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β

doi: 10.1038/s41420-026-02984-5

Figure Lengend Snippet: a MRI images, changes in AFP, and quantification of tumor volume in representative HCC-resistant patients before and after apatinib treatment. Scale bars, 10 cm. b MRI images, changes in AFP, and quantification of tumor thrombus volume in representative HCC-sensitive patients before and after apatinib treatment. Scale bars, 10 cm. c The GO pathway analysis of differential genes was enriched, with APOA2 ranking first in the small molecule metabolic process. d The KEGG pathway analysis of differential genes was enriched, with APOA2 ranking first in the PPAR signaling pathway. e Intensity of APOA2 IHC staining in 10 paired HCC patient tissues (sensitive vs resistant). Scale bars, 50 µm. f Predicted network diagram of the interactions between APOA2 and VEGFR2.

Article Snippet: Primary APOA2 antibody (Proteintech, 16845-1-AP, CHN) was diluted at 1:50, while mouse/rabbit linker (Santa Cruz, sc2357, USA) was diluted at 1:100.

Techniques: Immunohistochemistry

Journal: Cell Death Discovery

Article Title: APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β

doi: 10.1038/s41420-026-02984-5

Figure Lengend Snippet: After the evaluation of acquired drug resistance, the HCC-bearing mice were divided into 3 groups: (C)control ( n = 7), (R)resistant ( n = 7), and (S)sensitive ( n = 24). a Quantification of subcutaneous tumor mass and volume in the three groups. Numbers 1–7 represent control group, 1–7 for resistance group, and 1–7 for sensitivity group. * p < 0.05, ns, not significant. b . Representative images of CD31 immunofluorescence staining of tumor tissue. The upper part of the image is a comprehensive view of CD31 staining of the entire tumor tissue section, while the bottom part shows CD31 staining under magnification. CD31 + microvessel signals were randomly quantified from 12 fields ( n = 7 mice in each group), Scale bars, 50 µm. * p < 0.05, ns, not significant. c and d . Western blotting of APOA2, VEGFR2, and P-VEGFR2 in tumor tissue ( n = 4). e Representative images of APOA2 IHC staining intensity of tumor tissue, Scale bars, 100 µm. The upper part of the image is a comprehensive view of APOA2 staining of the entire tumor tissue section, while the bottom part shows APOA2 staining under magnification. Scale bars, 100 µm. * p < 0.05, ns, not significant.

Article Snippet: Primary APOA2 antibody (Proteintech, 16845-1-AP, CHN) was diluted at 1:50, while mouse/rabbit linker (Santa Cruz, sc2357, USA) was diluted at 1:100.

Techniques: Control, Immunofluorescence, Staining, Western Blot, Immunohistochemistry

Journal: Cell Death Discovery

Article Title: APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β

doi: 10.1038/s41420-026-02984-5

Figure Lengend Snippet: a Representative images of HCC cell lines overexpressing APOA2. Scale bars, 100 µm. Western blotting verified the protein levels of APOA2, VEGFR2, and P-VEGFR2 in 4 cell lines. b – d Subcutaneous tumor, tumor volume and tumor mass quantification, along with tumor growth curve of each group ( n = 6). e – g Characterization of tumor inhibition rate in each group. *** p < 0.001, **** p < 0.0001, ns not significant.

Article Snippet: Primary APOA2 antibody (Proteintech, 16845-1-AP, CHN) was diluted at 1:50, while mouse/rabbit linker (Santa Cruz, sc2357, USA) was diluted at 1:100.

Techniques: Western Blot, Inhibition

Journal: Cell Death Discovery

Article Title: APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β

doi: 10.1038/s41420-026-02984-5

Figure Lengend Snippet: a – f The experiment comprised two groups: control (Control) and APOA2 overexpression (APOA2). a , d Colony formation assay conducted on MHCC97H and SMMC7721 cells ( n = 3), b , e Representative images from EdU assay performed on MHCC97H and SMMC7721 cells, with EdU signals quantified from 12 fields ( n = 6), Scale bars, 50 µm. c , f CCK8 assay results of MHCC97H and SMMC7721 cells. g The experiment comprised 4 groups: control group receiving solvent and apatinib (Control + Vehicle vs Control + Apatinib), and the APOA2 overexpression group receiving solvent and apatinib (APOA2+Vehicle vs APOA2+Apatinib). Representative images of Ki67 and cleaved-caspase 3 immunofluorescence staining of tumor tissue, with Ki67+ and cleaved-caspase 3+ signals quantified from 12 fields ( n = 6). Scale bars, 100 µm. * p < 0.05, ns not significant.

Article Snippet: Primary APOA2 antibody (Proteintech, 16845-1-AP, CHN) was diluted at 1:50, while mouse/rabbit linker (Santa Cruz, sc2357, USA) was diluted at 1:100.

Techniques: Control, Over Expression, Colony Assay, EdU Assay, CCK-8 Assay, Solvent, Immunofluorescence, Staining

Journal: Cell Death Discovery

Article Title: APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β

doi: 10.1038/s41420-026-02984-5

Figure Lengend Snippet: a Representative bright-field images of tubular formation in HUVECs cultured with conditioned media from MHCC97H and SMCC7721 (overexpressing APOA2 or not). Scale bar, 400 µm. b Representative images of EdU assay conducted on HUVECs cultured with conditioned media from MHCC97H and SMCC7721 (overexpressing APOA2 or not), with EdU signals quantified from 12 fields ( n = 6). Scale bars, 100 µm. c Representative images of migration of HUVECs cultured with conditioned media from MHCC97H and SMCC7721 (overexpressing APOA2 or not), Scale bars, 100 µm. * p < 0.05, ns not significant.

Article Snippet: Primary APOA2 antibody (Proteintech, 16845-1-AP, CHN) was diluted at 1:50, while mouse/rabbit linker (Santa Cruz, sc2357, USA) was diluted at 1:100.

Techniques: Cell Culture, EdU Assay, Migration

Journal: Cell Death Discovery

Article Title: APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β

doi: 10.1038/s41420-026-02984-5

Figure Lengend Snippet: a Volcano plot of differentially expressed proteins between the APOA2 overexpression group and the control group, with a fold change ≥ 1.5 and adjusted p < 0.01 ( n = 3). Gray denotes no significant difference, blue indicates low expression, and red indicates high expression. The volcano plot labels the five highest expressed proteins and five lowest expressed proteins. b Histogram of 5 highest expressed proteins and 5 lowest expressed proteins ( n = 3). c Enrichment analysis of KEGG pathways for differentially expressed proteins between the APOA2 overexpression group and the control group. d Histogram showing levels of TGF-β ligand, receptor, and signaling pathway-related protein in proteomics (n = 3). e Pearson correlation analysis of five highly expressed proteins and TGF-β in HCC. f Relative mRNA levels of TGF-β in HCC cells and tumor tissues with or without overexpressing APOA2 analyzed by real-time quantitative PCR ( n = 6). g ELISA detection of TGF-β in HCC cell (with or without overexpressing APOA2) medium and serum of HCC-bearing mice (with or without overexpressing APOA2). h Western blotting detecting the protein levels of TGF-βR1, TGF-βR2, P-TGFβR1 and P-TGFβR2 in HCC cells and tumor tissues with or without overexpressing APOA2. * p < 0.05, ns, not significant.

Article Snippet: Primary APOA2 antibody (Proteintech, 16845-1-AP, CHN) was diluted at 1:50, while mouse/rabbit linker (Santa Cruz, sc2357, USA) was diluted at 1:100.

Techniques: Over Expression, Control, Expressing, Real-time Polymerase Chain Reaction, Enzyme-linked Immunosorbent Assay, Western Blot

Journal: Cell Death Discovery

Article Title: APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β

doi: 10.1038/s41420-026-02984-5

Figure Lengend Snippet: a Enrichment analysis of GO pathways for differentially expressed proteins between APOA2 overexpression and the control group, with a fold change ≥ 1.5 and adjusted p -value < 0.01. b Glucose consumption in MHCC97H cells in the designated group ( n = 6). c Lactate production in MHCC97H cells in the designated group ( n = 6). d Mito Fuel Flex test revealed dependence on the oxidation of glucose, glutamine, or FA in MHCC97H cells in the designated group ( n = 6). e BODIPY-FA uptake in MHCC97H cells in the designated group. f β-oxidation assay in MHCC97H cells in the designated group ( n = 6). g Intracellular ATP levels in MHCC97H cells in the designated group ( n = 6). * p < 0.05, ns not significant.

Article Snippet: Primary APOA2 antibody (Proteintech, 16845-1-AP, CHN) was diluted at 1:50, while mouse/rabbit linker (Santa Cruz, sc2357, USA) was diluted at 1:100.

Techniques: Over Expression, Control, Oxidation Assay