细胞凋亡
未折叠蛋白反应
乳腺癌
激酶
癌症研究
雌激素受体
基因敲除
癌细胞
内质网
切碎
癌症
化学
医学
生物
细胞生物学
内科学
生物化学
作者
Qiuya Wu,Duanfang Zhou,Zhengze Shen,Bo Chen,Gang Wang,Lihong Wu,Limei Zhang,Xiaoli Li,Lie Yuan,Yuanli Wu,Na Qu,Weiying Zhou
标识
DOI:10.1016/j.bcp.2023.115634
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.
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