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葫芦素E通过丝切蛋白-1和mTORC1诱导人前列腺癌细胞凋亡。

Cucurbitacin E induces apoptosis of human prostate cancer cells via cofilin-1 and mTORC1.

作者信息

He Xiaolong, Gao Qi, Qiang Yayong, Guo Wei, Ma Yadong

机构信息

Department of Urology, Yan'an University Affiliated Hospital, Yan'an, Shaanxi 716000, P.R. China.

出版信息

Oncol Lett. 2017 Jun;13(6):4905-4910. doi: 10.3892/ol.2017.6086. Epub 2017 Apr 24.

DOI:10.3892/ol.2017.6086
PMID:28599494
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5453063/
Abstract

Cucurbitacin E is an important member of the cucurbitacin family and exhibits inhibitory effects in various types of cancer. Cucurbitacin is a potential antineoplastic drug; however, its anticancer effect in human prostate cancer (PC) remains unknown. The aim of the present study was to determine whether the effect of cucurbitacin E on the cell viability and apoptosis of the human PC cell line, LNCaP, was mediated by cofilin-1- and mammalian target of rapamycin (mTOR). The results of the present study demonstrated that cucurbitacin E significantly exhibited cytotoxicity, suppressed cell viability (P<0.0001) and induced apoptosis (P=0.0082) in LNCaP cells. In addition, it was demonstrated that treatment with cucurbitacin E significantly induced cofilin-1 (P=0.0031), p-mTOR (P=0.0022), AMP-activated protein kinase (AMPK; P=0.0048), cellular tumor antigen p53 (p53; P=0.0018) and caspase-9 (P=0.0026) protein expression in LNCaP cells, suggesting that cucurbitacin E exerts its effects on LNCaP cells through cofilin-1, mTOR, AMPK, p53 and caspase-9 signaling. These results suggested that cucurbitacin E maybe used as a therapeutic agent in the treatment of human PC.

摘要

葫芦素E是葫芦素家族的重要成员,对多种癌症具有抑制作用。葫芦素是一种潜在的抗肿瘤药物;然而,其对人前列腺癌(PC)的抗癌作用尚不清楚。本研究的目的是确定葫芦素E对人PC细胞系LNCaP的细胞活力和凋亡的影响是否由丝切蛋白-1和雷帕霉素哺乳动物靶蛋白(mTOR)介导。本研究结果表明,葫芦素E在LNCaP细胞中显著表现出细胞毒性,抑制细胞活力(P<0.0001)并诱导凋亡(P=0.0082)。此外,结果表明,用葫芦素E处理可显著诱导LNCaP细胞中丝切蛋白-1(P=0.0031)、磷酸化mTOR(p-mTOR;P=0.0022)、AMP活化蛋白激酶(AMPK;P=0.0048)、细胞肿瘤抗原p53(p53;P=0.0018)和半胱天冬酶-9(P=0.0026)的蛋白表达,提示葫芦素E通过丝切蛋白-1、mTOR、AMPK、p53和半胱天冬酶-9信号通路对LNCaP细胞发挥作用。这些结果表明,葫芦素E可能用作治疗人PC的治疗剂。

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