Resveratrol Enhances the Chemotherapeutic Response and Reverses the Stemness Induced by Gemcitabine in Pancreatic Cancer Cells Via Targeting SREBP1

Overview

Journal Cell Prolif

Date 2018 Oct 21

PMID 30341797

Citations 38

Authors

Cancan Zhou

Weikun Qian

Jiguang Ma

Liang Cheng

Zhengdong Jiang

Bin Yan

Jie Li

Wanxing Duan

Liankang Sun

Junyu Cao

Fengfei Wang

Erxi Wu

Zheng Wu

Qingyong Ma

Xuqi Li

Affiliations

Soon will be listed here.

Abstract

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 (SREBP1) 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 SREBP1. Knockdown of SREBP1 limited the sphere formation ability and suppressed the expression of CSC markers. Furthermore, suppression of SREBP1 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 SREBP1 both in vitro and in vivo. Thus, resveratrol can be an effective chemotherapy sensitizer, and SREBP1 may be a rational therapeutic target.

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