薯蓣皂苷元通过腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白通路增强前列腺癌细胞放疗敏感性的实验研究  

An experimental study of diosgenin enhancing the radiotherapy sensitivity of prostate cancer cells through AMPK/mTOR pathway

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作  者:徐林飞[1] 刘晟[1] 林勇峰 林星长 XU Linfei;LIU Sheng;LIN Yongfeng;LIN Xingzhang(Department of Urology,Taizhou Municipal Hospital,Taizhou 318000,Zhejiang,China)

机构地区:[1]台州市立医院泌尿外科,浙江台州318000

出  处:《中国性科学》2022年第12期34-39,共6页Chinese Journal of Human Sexuality

基  金:浙江省自然科学基金(Y12H050048);2020年浙江省台州市科技局项目(20ywa33)。

摘  要:目的探究薯蓣皂苷元(DG)增强前列腺癌(PCa)细胞放疗敏感性的作用机制。方法CCK-8检测细胞增殖活力;集落形成实验检测细胞集落形成率;酶联免疫吸附试验检测细胞乳酸脱氢酶(LDH)漏出率;流式细胞仪检测细胞凋亡率;免疫荧光分析细胞中γH2AX焦点形成数;免疫印迹分析细胞中增殖、凋亡及腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白(AMPK/mTOR)通路相关蛋白的表达。结果当X线(IR)≥4Gy、DG≥25μM时,PCa细胞增殖活力被明显抑制(P<0.05)。DG干预可有效改善IR处理对PCa细胞增殖能力、LDH漏出率、细胞凋亡、γH2AX焦点形成数及AMPK/mTOR通路相关蛋白的影响。AMPK抑制剂Compound C具有与DG相反的效果,且可部分逆转DG对以上指标的影响(P<0.05)。结论DG通过激活AMPK/mTOR通路增强PCa细胞放疗敏感性。Objective To explore the mechanism of diosgenin(DG)enhancing the radiotherapy sensitivity of prostate cancer(PCa)cells.Methods Cell proliferation activity was detected by CCK-8.Colony formation rate was detected by colony formation assay.Lactate dehydrogenase(LDH)leakage rate was detected by enzyme-linked immunosorbent assay.Apoptosis rate was detected by flow cytometry.Immunofluorescence analysis of the number of foci of phosphorylated histone H2AX(γH2AX)in cells.Western blot analysis of proliferation,apoptosis and adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)in cells expression of pathway-related proteins.Results When X-irradiation(IR)≥4Gy,DG≥25μM,the proliferation of PCa cells was significantly inhibited(P<0.05).DG intervention could effectively improve the effects of IR treatment on PCa cell proliferation ability,LDH leakage rate,apoptosis,γH2AX foci formation number,and AMPK/mTOR pathway-related proteins.The AMPK inhibitor Compound C has the opposite effect of DG and could partially reverse the effect of DG on the above indicators(P<0.05).Conclusions DG enhances the radiotherapy sensitivity of PCa cells by activating the AMPK/mTOR pathway.

关 键 词:薯蓣皂苷元 前列腺癌 腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白通路 放疗敏感性 

分 类 号:R697[医药卫生—泌尿科学]

 

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