Journal: Cancer Research

Article Title: Inhibiting Fatty Acid Oxidation Reverses Autophagy-Mediated Acquired Chemotherapy Resistance in Pancreatic Ductal Adenocarcinoma

doi: 10.1158/0008-5472.CAN-25-4517

Figure Lengend Snippet: Autophagy depends on JNK1-induced Beclin-1 activation. A, Pancreatic cancer cell lines MIA PaCa-2 and SU.86.86 were treated with IR (1 μmol/L) for immunoblotting. B, Immunoblot analysis of late-stage autophagy in MIA PaCa-2. ULK1 inhibitor (ULK1i, XST-14, 5 μmol/L; ref. ) and JNK1 inhibitor (JNK1i, SP600125, 20 μmol/L; refs. , ) were administered individually or in combination 48 hours after IR treatment and were maintained for an additional 24 hours. Cell lysates were collected at the 72-hour time point for immunoblotting and ATP assay. Data are shown as the mean ± SD from n = 3 independent experiments. C, co-IP analysis of the Bcl-2 complex in MIA PaCa-2 and SU.86.86 cells treated with IR (1 μmol/L) for 0, 24, 48, and 72 hours. Cell lysates were immunoprecipitated with an anti–Bcl-2 antibody (IP: Bcl-2), and Bcl-2-bound Beclin-1 and Bax were detected by immunoblotting (IB: Beclin-1, Bax). Quantification represents Beclin-1 coimmunoprecipitated with Bcl-2, normalized to immunoprecipitated Bcl-2 (Beclin-1/Bcl-2), and expressed relative to 0 hours (set to 1). Whole-cell lysates (input) from the same samples were analyzed by immunoblotting to determine p-Bcl-2 levels and total Bcl-2, as indicated. Quantification represents p-Bcl-2/total Bcl-2, expressed relative to 0 hours (set to 1). Data are shown as the mean ± SD from n = 3 independent experiments. Statistical comparisons vs. 0 hours were performed using one-way ANOVA. co-IP, coimmunoprecipitation; Ct, control; IR, irinotecan. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; ns, not significant.

Article Snippet: MIA PaCa-2 cells were treated with irinotecan (1 μmol/L) for 48 hours, followed by treatment with the ULK1 inhibitor XST-14 (5 μmol/L; MedChemExpress, Monmouth Junction; ref. ) or the JNK1 inhibitor SP600125 (20 μmol/L; MedChemExpress, Monmouth Junction; refs. , ) for an additional 24 hours.

Techniques: Activation Assay, Western Blot, ATP Assay, Co-Immunoprecipitation Assay, Immunoprecipitation, Control

Journal: Cancer Research

Article Title: Inhibiting Fatty Acid Oxidation Reverses Autophagy-Mediated Acquired Chemotherapy Resistance in Pancreatic Ductal Adenocarcinoma

doi: 10.1158/0008-5472.CAN-25-4517

Figure Lengend Snippet: The development model of acquired drug resistance by drug treatment. A, When cancer cells are treated with cytotoxic anticancer drugs, they experience cellular stress such as DNA damage, which activates AMPK-dependent early autophagy. At this stage, cells with severe damage undergo autophagic cell death, whereas surviving cells supply FAs via autophagy. B, When cancer cells face sustained stress from anticancer drugs, FAO is activated, leading to increased ATP production. This increase in ATP inactivates AMPK-dependent autophagy and activates mTOR. However, cancer cells also activate JNK1-dependent late autophagy in response to cellular damage, maintaining mTOR activity through FAO. This process results in tumor regrowth during treatment with anticancer drugs. A key feature of this stage is that autophagy and mTOR, which normally inhibit each other via feedback mechanisms, are concurrently activated through independent pathways due to damage caused by anticancer drugs. C, Both AMPK-dependent and JNK1-dependent autophagy promote mTOR activation through FAO induction. Therefore, anticancer drugs combined with FAO-inhibiting drugs induce cell death by inactivating mTOR survival signals and promoting autophagy flux but impairing autolysis due to FA deposits. In this study, we demonstrated this concept by double knockdown of CAC and ACAA1 , the main FAO pathways, or using KN510713 , FAO inhibitors. FA, fatty acid.

Article Snippet: MIA PaCa-2 cells were treated with irinotecan (1 μmol/L) for 48 hours, followed by treatment with the ULK1 inhibitor XST-14 (5 μmol/L; MedChemExpress, Monmouth Junction; ref. ) or the JNK1 inhibitor SP600125 (20 μmol/L; MedChemExpress, Monmouth Junction; refs. , ) for an additional 24 hours.

Techniques: Activity Assay, Activation Assay, Knockdown

Journal: Poultry Science

Article Title: Cadmium-induced apoptosis via ROS/JNK pathway in chicken primary kidney cells and antagonism of taxifolin

doi: 10.1016/j.psj.2026.106920

Figure Lengend Snippet: Effect of Tax on gene expression of the JNK pathway in Cd-induced apoptosis of chicken primary kidney cells. (A) Molecular docking results between Tax and JNK. (B) Cellular Thermal Shift Assay to verify the interaction between Tax and JNK. (C) Relative protein expression of p-JNK/JNK and relative mRNA expression of JNK. * Indicates a significant difference between DMSO group and Cd group (n=10; * P < 0.05). # Indicates a significant difference between Cd + Tax group and Cd group ( n = 10; # P < 0.05). Results are presented as mean ± SEM. Statistical significance was determined by one-way ANOVA or unpaired Student’s t-test.

Article Snippet: p-JNK , Wanleibio , 1:500 , WL01813.

Techniques: Gene Expression, Thermal Shift Assay, Expressing

Journal: Poultry Science

Article Title: Cadmium-induced apoptosis via ROS/JNK pathway in chicken primary kidney cells and antagonism of taxifolin

doi: 10.1016/j.psj.2026.106920

Figure Lengend Snippet: The protein levels of cells treated with SP600125 and NAC. (A) Protein expression of p-JNK/JNK, Bad, Bid, Bcl-2, Bax, Bak, DIABLO, XIAP, Caspase-3, and Caspase-9. (B) Quantitative analysis of p-JNK/JNK, Bad, Bid, Bcl-2, Bax, Bak, DIABLO, XIAP, Caspase-3, and Caspase-9 expression. Data are presented as mean ± SD (n = 10). * Indicates a significant difference on Cd + SP600125 or Cd + NAC vs Cd group ( n = 10; * P < 0.05). # Indicates a significant difference between Cd + SP600125 + Tax group and Cd + Tax group ( n = 10; # P < 0.05).

Article Snippet: p-JNK , Wanleibio , 1:500 , WL01813.

Techniques: Expressing