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水菖蒲碱通过调控 PI3K/AKT/mTOR 信号通路抑制炎症和细胞增殖促进宫颈癌(ME-180)细胞凋亡。

Brucine promotes apoptosis in cervical cancer cells (ME-180) via suppression of inflammation and cell proliferation by regulating PI3K/AKT/mTOR signaling pathway.

机构信息

Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdul Aziz University, Al-Kharj, Saudi Arabia.

出版信息

Environ Toxicol. 2021 Sep;36(9):1841-1847. doi: 10.1002/tox.23304. Epub 2021 Jun 2.

Abstract

Brucine are the main constituents of Strychnos nux-vomica. Earlier reports have determined brucine shows anti-inflammatory, analgesic and excellent anti-tumor drug. Even though its anticervical cancer cells remains not clearly evaluated. So that, we hypothesized the anti-cervical cancer activity of brucine against the cervical (ME-180) cells. Brucine inhibited the inflammation, cell proliferation and promoted rate of apoptotic cell death ad reduced the mitochondrial potential, which is evidenced by respective (AO/EB, Rh-123, and PI) staining. Furthermore ELISA and real time PCR reaction determined that brucine were down regulated inflammatory (TNF-α, NF-kB, IL-6 & COX-2) cell proliferation (Cyclin D1) and apoptotic marker Bax, caspase-3, PI3K (phosphoinosital 3 kinase), AKT, mTOR (mammalian target of rapamycin) and over expression Bcl-2, associated death promoter. These findings were confirmed and finally suggested that brucine inhibited inflammation, cell proliferation and promoted the apoptosis through the down-regulation of PI3K/AKT/mTOR pathway. Taken together, these data were exhibited brucine as a good therapeutic agents for the prevention of anticancer cervical cancer drugs.

摘要

马钱子碱是马钱子的主要成分。早期的报告已经确定马钱子碱具有抗炎、镇痛和极好的抗肿瘤作用。尽管其抗宫颈癌作用尚未得到明确评估。因此,我们假设马钱子碱对宫颈癌(ME-180)细胞具有抗癌活性。马钱子碱抑制炎症、细胞增殖,并促进细胞凋亡,降低线粒体膜电位,这一点可以通过相应的(AO/EB、Rh-123 和 PI)染色来证明。此外,ELISA 和实时 PCR 反应确定马钱子碱下调了炎症(TNF-α、NF-kB、IL-6 和 COX-2)、细胞增殖(Cyclin D1)和凋亡标志物 Bax、caspase-3、PI3K(磷酸肌醇 3 激酶)、AKT、mTOR(雷帕霉素的哺乳动物靶标),并上调了与死亡促进相关的 Bcl-2。这些发现得到了证实,并最终表明马钱子碱通过下调 PI3K/AKT/mTOR 通路抑制炎症、细胞增殖并促进细胞凋亡。总之,这些数据表明马钱子碱作为一种预防抗癌宫颈癌药物的良好治疗剂。

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