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葛根素通过mTOR/p70S6K信号通路抑制膀胱癌细胞增殖。

Puerarin inhibits bladder cancer cell proliferation through the mTOR/p70S6K signaling pathway.

作者信息

Jiang Kehua, Chen Hongbo, Tang Kun, Guan Wei, Zhou Hui, Guo Xiaolin, Chen Zhiqiang, Ye Zhangqun, Xu Hua

机构信息

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Department of Urology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, P.R. China.

出版信息

Oncol Lett. 2018 Jan;15(1):167-174. doi: 10.3892/ol.2017.7298. Epub 2017 Oct 31.

DOI:10.3892/ol.2017.7298
PMID:29375709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5766064/
Abstract

Puerarin, as a novel oncotherapeutic agent, may exert anticancer effects and inhibit the proliferation of cancer cells. To explore the effects of puerarin on human bladder cancer cells, and to elucidate the potential mechanism underlying these effects, a Cell Counting Kit-8 assay was used to examine the proliferation of T24 and EJ cells following puerarin treatment. The effects of puerarin treatment on the cell cycle were detected by flow cytometry (FCM), while puerarin-induced cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling and FCM, and the cellular ultrastructural morphological changes were observed by transmission electron microscopy. Cell invasion was examined using a Transwell assay with Matrigel. The expression levels of mechanistic target of rapamycin (mTOR), phosphorylated (p)-mTOR, p70-S6 kinase (p70S6K) and p-p70S6K proteins in the mTOR signaling pathway were then assessed by western blotting. The results demonstrated that puerarin may inhibit bladder cancer cell viability, block the cell cycle in the G0/G1 phase and induce apoptosis in bladder cancer cells. The expression levels of p-mTOR and p-p70S6K proteins were downregulated, while no change was observed in the expression levels of mTOR and p70S6K proteins when T-24 and EJ cells were treated by puerarin. In the present study, puerarin was demonstrated to inhibit the viability of human bladder cancer cells. These effects may be due to the puerarin-induced downregulation of proteins in the mTOR/p70S6K signaling pathway, and the present study may provide the experimental basis for puerarin to be considered as a promising novel anti-tumor drug for the treatment of bladder cancer.

摘要

葛根素作为一种新型的肿瘤治疗药物,可能具有抗癌作用并抑制癌细胞增殖。为了探究葛根素对人膀胱癌细胞的影响,并阐明其潜在机制,采用细胞计数试剂盒-8法检测葛根素处理后T24和EJ细胞的增殖情况。通过流式细胞术(FCM)检测葛根素处理对细胞周期的影响,同时采用末端脱氧核苷酸转移酶dUTP缺口末端标记法和FCM检测葛根素诱导的细胞凋亡,并通过透射电子显微镜观察细胞超微结构形态变化。使用基质胶Transwell实验检测细胞侵袭能力。然后通过蛋白质印迹法评估雷帕霉素靶蛋白(mTOR)、磷酸化(p)-mTOR、p70-S6激酶(p70S6K)和p-p70S6K蛋白在mTOR信号通路中的表达水平。结果表明,葛根素可能抑制膀胱癌细胞活力,将细胞周期阻滞在G0/G1期,并诱导膀胱癌细胞凋亡。当T-24和EJ细胞用葛根素处理时,p-mTOR和p-p70S6K蛋白的表达水平下调,而mTOR和p70S6K蛋白的表达水平未观察到变化。在本研究中,葛根素被证明可抑制人膀胱癌细胞的活力。这些作用可能归因于葛根素诱导的mTOR/p70S6K信号通路中蛋白表达下调,本研究可能为葛根素被视为一种有前景的新型抗肿瘤药物用于治疗膀胱癌提供实验依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/7e2af166a571/ol-15-01-0167-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/b12e657b6b3a/ol-15-01-0167-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/f73c24e922ee/ol-15-01-0167-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/bf5a8a5dc4a2/ol-15-01-0167-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/6e784856826e/ol-15-01-0167-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/516f058410d6/ol-15-01-0167-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/7e2af166a571/ol-15-01-0167-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/b12e657b6b3a/ol-15-01-0167-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/f73c24e922ee/ol-15-01-0167-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/bf5a8a5dc4a2/ol-15-01-0167-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/6e784856826e/ol-15-01-0167-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/516f058410d6/ol-15-01-0167-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21aa/5766064/7e2af166a571/ol-15-01-0167-g05.jpg

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