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Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1

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 me...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430460/
https://www.ncbi.nlm.nih.gov/pubmed/30341797
http://dx.doi.org/10.1111/cpr.12514
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author 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
author_facet 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
author_sort Zhou, Cancan
collection PubMed
description 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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spelling pubmed-64304602020-03-13 Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1 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 Cell Prolif Original Articles 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. John Wiley and Sons Inc. 2018-10-19 /pmc/articles/PMC6430460/ /pubmed/30341797 http://dx.doi.org/10.1111/cpr.12514 Text en © 2018 The Authors Cell Proliferation Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
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
Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1
title Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1
title_full Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1
title_fullStr Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1
title_full_unstemmed Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1
title_short Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1
title_sort resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting srebp1
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430460/
https://www.ncbi.nlm.nih.gov/pubmed/30341797
http://dx.doi.org/10.1111/cpr.12514
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