白藜芦醇通过抑制PARP1促进胰腺癌对吉西他滨的化疗敏感性

Objective: To investigate the effects of resveratrol on gemcitabine chemotherapy in pancreatic cancer and the possible molecular mechanism. Methods: Gemcitabine resistant cell lines were screened by continuous low concentration increasing induction. High-throughput RNA-seq was used to analyze the differential expression enrichment pathway, COMET assay was used to detect DNA damage, Western blotting was used to detect related pathway indicators, and Chou-Talalay was used to calculate drug combination synergistic index. AutoDock predicts docking targets for small molecules and proteins. Results: DNA damage repair related pathways were activated in drug-resistant cell lines compared with their parents. Resveratrol enhanced the DNA damage effects induced by gemcitabine (P<0.01). Resveratrol inhibited the expression of PARP1, a key molecule of DNA damage repair, and played a synergic effect with gemcitabine (CI<1). Resveratrol has docking targets with the CAT domain of PARP1. Conclusion: Resveratrol can inhibit PARP1, a key molecule of chemotherapy resistance, and has a synergistic effect with gemcitabine in pancreatic cancer chemotherapy.