VPS34-IN1 induces apoptosis of ER plus breast cancer cells via activating PERK/ATF4/CHOP pathway

作者全名："Wu, Qiuya; Zhou, Duanfang; Shen, Zhengze; Chen, Bo; Wang, Gang; Wu, Lihong; Zhang, Limei; Li, Xiaoli; Yuan, Lie; Wu, Yuanli; Qu, Na; Zhou, Weiying"

作者地址："[Wu, Qiuya; Zhou, Duanfang; Chen, Bo; Wang, Gang; Wu, Lihong; Zhang, Limei; Li, Xiaoli; Yuan, Lie; Wu, Yuanli; Qu, Na; Zhou, Weiying] Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing 400016, Peoples R China; [Wu, Qiuya; Zhou, Duanfang; Chen, Bo; Wang, Gang; Wu, Lihong; Zhang, Limei; Li, Xiaoli; Yuan, Lie; Wu, Yuanli; Qu, Na; Zhou, Weiying] Chongqing Med Univ, Chongqing Key Lab Drug Metab, Chongqing 400016, Peoples R China; [Li, Xiaoli; Zhou, Weiying] Chongqing Med Univ, Key Lab Biochem & Mol Pharmacol Chongqing, Chongqing 400016, Peoples R China; [Shen, Zhengze] Chongqing Med Univ, Dept Pharm, Yongchuan Hosp, 439 Xuanhua Rd, Chongqing 402160, Peoples R China"

通信作者："Zhou, WY (通讯作者)，Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing 400016, Peoples R China."

来源：BIOCHEMICAL PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001022615400001

JCR分区：Q1

影响因子：5.3

年份：2023

卷号：214

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：VPS34-IN1; Breast cancer; ER stress; Apoptosis; PI3K

摘要："VPS34-IN1 is a specific selective inhibitor of Class III Phosphatidylinositol 3-kinase (PI3K) and has been shown to exhibit a significant antitumor effect in leukemia and liver cancer. In current study, we focused on the anticancer effect and potential mechanism of VPS34-IN1 in estrogen receptor positive (ER+ ) breast cancer. Our results revealed that VPS34-IN1 inhibited the viability of ER+ breast cancer cells in vitro and in vivo. Flow cytometry and western blot analyses showed that VPS34-IN1 treatment induced breast cancer cell apopotosis. Interestingly, VPS34-IN1 treatment activated protein kinase R (PKR)-like ER kinase (PERK) branch of endoplasmic reticulum (ER) stress. Furthermore, knockdown of PERK by siRNA or inhibition of PERK activity by chemical inhibitor GSK2656157 could attenuate VPS34-IN1-mediated apoptosis in ER+ breast cancer cells. Collectively, VPS34-IN1 has an antitumor effect in breast cancer, and it may result from activating PERK/ATF4/CHOP pathway of ER stress to induce cell apoptosis. These findings broaden our understanding of the anti-breast cancer effects and mechanisms of VPS34-IN1 and provide new ideas and reference directions for the treatment of ER+ breast cancer."

基金机构：National Natural Science Founda- tion of China [81874100]; Innovation research group in Colleges and Universities Program of Chongqing Municipal Education Commission [CXQT20012]; CQMU Program for Youth Innovation in Future Medicine [W0067]; High-level Young Scientific and Technological Talent Cultivation Program of Chongqing Medical University; Top-notch Postgraduate Talent Cultivation program of Chongqing Medical University [BJRC202106]

基金资助正文：This research was funded by the National Natural Science Founda- tion of China (No.81874100) ; Innovation research group in Colleges and Universities Program of Chongqing Municipal Education Commission (No. CXQT20012) ; CQMU Program for Youth Innovation in Future Medicine (W0067) ; High-level Young Scientific and Technological Talent Cultivation Program of Chongqing Medical University; Top-notch Postgraduate Talent Cultivation program of Chongqing Medical University (No. BJRC202106) .