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葛根素通过抑制PI3K/mTOR信号通路抑制人乳头瘤病毒阳性宫颈癌细胞的生长和迁移。

Puerarin suppresses cell growth and migration in HPV-positive cervical cancer cells by inhibiting the PI3K/mTOR signaling pathway.

作者信息

Jia Lihua, Hu Yuling, Yang Guohua, Li Peiling

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

Department of Obstetrics and Gynecology, Tongzhou Maternal and Child Health Hospital of Beijing, Beijing 101101, P.R. China.

出版信息

Exp Ther Med. 2019 Jul;18(1):543-549. doi: 10.3892/etm.2019.7589. Epub 2019 May 17.

Abstract

Puerarin is an effective component that is present in high concentrations in the plant and is extensively distributed throughout nature. Puerarin possesses a number of pharmacological effects and has strong pharmacological activity with few side effects and extensive clinical applications. The aim of the present study was to explore the effects of Puerarin on the apoptosis of human papillomavirus (HPV)-positive cervical cancer cells and the underlying molecular mechanisms. MTT assay, lactate dehydrogenase activity and Annexin V/fluorescein isothiocyanate/propidium iodide analysis were used to analyze cell growth of HPV-positive HeLa cervical cancer cells treated with Puerarin. Western blotting was performed to measure protein expression in the treated cells. Puerarin significantly reduced cell proliferation and induced apoptosis in HeLa cells. In addition, it was observed that Puerarin significantly enhanced caspase-3/9 activities and significantly increased B-cell lymphoma 2-asscoiate X protein expression in HeLa cells. Puerarin suppressed phosphatidylinositol-3 kinase (PI3K), phosphorylated (p)-protein kinase B (Akt) and p-mammalian target of rapamycin (mTOR) protein expression in HeLa cells. These results indicate that Puerarin induces apoptosis in HPV-positive HeLa cervical cancer cells via inhibiting PI3K/Akt/mTOR signaling.

摘要

葛根素是一种在植物中高浓度存在且广泛分布于自然界的有效成分。葛根素具有多种药理作用,药理活性强,副作用少,临床应用广泛。本研究的目的是探讨葛根素对人乳头瘤病毒(HPV)阳性宫颈癌细胞凋亡的影响及其潜在的分子机制。采用MTT法、乳酸脱氢酶活性检测及膜联蛋白V/异硫氰酸荧光素/碘化丙啶分析,分析葛根素处理的HPV阳性HeLa宫颈癌细胞的生长情况。采用蛋白质印迹法检测处理后细胞中的蛋白质表达。葛根素显著降低HeLa细胞的增殖并诱导其凋亡。此外,观察到葛根素显著增强HeLa细胞中半胱天冬酶-3/9的活性,并显著增加B细胞淋巴瘤2相关X蛋白的表达。葛根素抑制HeLa细胞中磷脂酰肌醇-3激酶(PI3K)、磷酸化蛋白激酶B(Akt)和磷酸化哺乳动物雷帕霉素靶蛋白(mTOR)的蛋白表达。这些结果表明,葛根素通过抑制PI3K/Akt/mTOR信号通路诱导HPV阳性HeLa宫颈癌细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c9d/6566033/8102f24bf375/etm-18-01-0543-g00.jpg

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