Synergistic effects of resveratrol with gemcitabine in pancreatic cancer chemotherapy by inhibiting PARP1

Shuai WU; Cancan Zhou; Liang Han; Qingyong MA; Zheng WU

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Synergistic effects of resveratrol with gemcitabine in pancreatic cancer chemotherapy by inhibiting PARP1

VernacularTitle: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
Author: Shuai WU ¹ ; Cancan ZHOU ¹ ; Liang HAN ¹ ; Qingyong MA ¹ ; Zheng WU ¹
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1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Publication Type:Journal Article
Keywords: pancreatic cancer; resveratrol; gemcitabine; PARP1; chemosensitization
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(6):850-855
CountryChina
Language:Chinese
Abstract: 【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.