Open AccessResveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP 1
Author(s) -
Zhou Cancan,
Qian Weikun,
Ma Jiguang,
Cheng Liang,
Jiang Zhengdong,
Yan Bin,
Li Jie,
Duan Wanxing,
Sun Liankang,
Cao Junyu,
Wang Fengfei,
Wu Erxi,
Wu Zheng,
Ma Qingyong,
Li Xuqi
Publication year - 2019
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12514
Subject(s) - gemcitabine , resveratrol , cancer research , pancreatic cancer , chemistry , gene knockdown , cancer , cancer cell , sterol regulatory element binding protein , pharmacology , flow cytometry , apoptosis , biology , medicine , biochemistry , cholesterol , microbiology and biotechnology , sterol
Objectives Gemcitabine is a standard treatment for advanced pancreatic cancer patients but can cause chemoresistance during treatment. The chemoresistant cells have features of cancer stem cells (CSCs). Resveratrol has been reported to overcome the resistance induced by gemcitabine. However, the mechanism by which resveratrol enhances chemosensitivity remains elusive. Here, we explored the mechanism by which resveratrol enhanced chemosensitivity and the role of sterol regulatory element binding protein 1 ( SREBP 1) in gemcitabine‐induced stemness. Materials and methods The pancreatic cancer cell lines MiaPaCa‐2 and Panc‐1 were treated under different conditions. Methyl thiazolyl tetrazolium and colony formation assays were performed to evaluate effects on proliferation. Flow cytometry was conducted to detect apoptosis. Oil red O staining was performed to examine lipid synthesis. The sphere formation assay was applied to investigate the stemness of cancer cells. Immunohistochemistry was performed on tumour tissue obtained from treated KPC mice. Results Resveratrol enhanced the sensitivity of gemcitabine and inhibited lipid synthesis via SREBP 1. Knockdown of SREBP 1 limited the sphere formation ability and suppressed the expression of CSC markers. Furthermore, suppression of SREBP 1 induced by resveratrol reversed the gemcitabine‐induced stemness. These results were validated in a KPC mouse model. Conclusions Our data provide evidence that resveratrol reverses the stemness induced by gemcitabine by targeting SREBP 1 both in vitro and in vivo. Thus, resveratrol can be an effective chemotherapy sensitizer, and SREBP 1 may be a rational therapeutic target.