基于ROS/PI3K/Akt/mTOR信号通路探讨玫瑰花甲醇提取物对前列腺癌PC-3细胞凋亡的影响  

Effects of apoptosis induced by methanolic extract of Rosa rugosa Thunb. in prostate cancer PC-3 cells based upon ROS/PI3K/Akt/mTOR signaling pathway

作　　者：严宝飞 刘嘉 刘圣金[2] 吴洁 刘梦梦 张景正 刘永琪 许虎 曾庆琪 YAN Bao-fei;LIU Jia;LIU Sheng-jin;WU Jie;LIU Meng-meng;ZHANG Jing-zheng;LIU Yong-qi;XU Hu;ZENG Qing-qi(Jiangsu Health Vocational College,Jiangsu Nanjing 211800,China;Nanjing University of Chinese Medicine,Jiangsu Nanjing 210023,China;First Hospital Affiliated to Nanjing University of Chinese Medicine,Jiangsu Nanjing 210029,China)

机构地区：[1]江苏卫生健康职业学院,江苏南京211800 [2]南京中医药大学,江苏南京210023 [3]南京中医药大学第一附属医院,江苏南京210029

出　　处：《中国医院药学杂志》2021年第19期1987-1992,共6页Chinese Journal of Hospital Pharmacy

基　　金：江苏省自然科学基金项目(编号:BK20191498);江苏省卫生健康委医学科研项目重点项目(编号:ZDB2020020);江苏省大学生创新创业计划(编号:201914255003Y);江苏卫生健康职业学院校级课题重点项目(编号:JKA201916)。

摘　　要：目的:探讨玫瑰花甲醇提取物(RE)对前列腺癌PC-3细胞增殖和凋亡的影响及潜在作用机制。方法:采用CCK8法检测不同浓度RE对PC-3细胞增殖的影响;采用Hoechst染色法和Annexin V/PI双染法检测细胞凋亡;DCFH-DA检测细胞ROS水平;Western blot法检测Bax、Bcl-2、cleaved caspase-3、Cyt-C、PI3K、p-PI3K、Akt、p-Akt、mTOR、p-mTOR的蛋白表达。结果:RE呈浓度依赖性抑制前列腺癌PC-3细胞增殖,24 h和48 h后的IC_(50)值分别为31.30 mg·mL^(-1)和16.76 mg·mL^(-1);RE能显著诱导PC-3细胞凋亡(P<0.05,P<0.01),且呈现浓度依赖性;RE可显著提高PC-3细胞ROS水平(P<0.05,P<0.01),且具有浓度依赖性;RE能显著上调PC-3细胞Bax、cleaved caspase-3、Cyt-C的蛋白表达及Bax/Bcl-2的比值(P<0.05,P<0.01),显著下调Bcl-2、p-PI3K、p-Akt、p-mTOR的蛋白表达(P<0.05,P<0.01),以上均呈现浓度依赖性。结论:本研究表明RE在体外有明显抑制前列腺癌细胞PC-3的增殖作用,并可能通过调控ROS/PI3K/Akt/mTOR信号通路诱导其凋亡,研究结果可为玫瑰花及其组方临床治疗前列腺癌提供实验依据。OBJECTIVE To explore the effects of methanolic extract of Rosa rugosa Thunb.(RE) on the proliferation and apoptosis of prostate cancer PC-3 cell and elucidate its potential mechanism.METHODS The effects of different concentrations of RE on cellular proliferation were detected by CCK8 assay. Apoptosis was detected by Hoechst staining and annexin V/PI double staining. The cellular level of reactive oxygen species(ROS) was measured by DCFH-DA. And Bax, Bcl-2, cleaved caspase-3, Cyt-C, PI3 K, p-PI3 K, Akt, p-Akt, mTOR and p-mTOR were detected by Western Blot.RESULTS RE suppressed cellular proliferation in a concentration-dependent manner and IC_(50) values were 31.30 and 16.76 mg·mL^(-1) at 24 h and 48 h. It could significantly induce cellular apoptosis in a concentration-dependent manner(P<0.05, P<0.01), elevate the cellular level of ROS in a concentration-dependent manner(P<0.05, P<0.01), up-regulate the protein expressions of Bax, cleaved caspase-3, Cyt-C, enhance the ratio of Bax/Bcl-2(P<0.05, P<0.01) and down-regulate the protein expressions of Bcl-2, p-PI3 K, p-Akt and p-mTOR in a concentration-dependent manner(P<0.05, P<0.01).CONCLUSION RE can significantly suppress the in vitro proliferation of prostate cancer PC-3 cell and induce apoptosis through regulating ROS/PI3 K/Akt/mTOR signaling pathway. The results of the study may provide experimental rationales for clinical treatment of prostate cancer with Rosa rugosa Thunb. and its formula.

关 键 词：玫瑰花 前列腺癌 增殖 凋亡 ROS/PI3K/Akt/mTOR信号通路 

分 类 号：R979.1[医药卫生—药品]