白花丹总皂苷通过抑制 PI3K/Akt/mTOR 通路对 MDA-MB-231 人乳腺癌细胞发挥抗肿瘤活性。

Total saponins of Bolbostemma paniculatum (maxim.) Franquet exert antitumor activity against MDA-MB-231 human breast cancer cells via inhibiting PI3K/Akt/mTOR pathway.

机构信息

School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, People's Republic of China.

Shaanxi Key Laboratory of "Qiyao" Resources And Anti-tumor Activities, Xi'an, Shaanxi, 710061, People's Republic of China.

出版信息

BMC Complement Altern Med. 2019 Nov 8;19(1):304. doi: 10.1186/s12906-019-2708-0.

DOI:10.1186/s12906-019-2708-0

PMID:31703679

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6842232/

Abstract

BACKGROUND

The aim of the present study was to examine the effects of the Bolbostemma paniculatum (Maxim.) Franquet (BP) active compound, BP total saponins (BPTS), on MDA-MB-231 cells, and investigate the underlying mechanism regarding BPTS-mediated attenuation of the PI3K/Akt/mTOR pathway.

METHODS

The effect of BPTS on cytotoxicity, induction of apoptosis and migration on MDA-MB-231 cells at three different concentrations was investigated. A CCK-8 assay, wound-healing assay and flow cytometry were used to demonstrate the effects of BPTS. Additionally, expression of the primary members of the PI3K/Akt/mTOR signaling pathway was assessed using western blotting. To verify the underlying mechanisms, a PI3K inhibitor and an mTOR inhibitor were used.

RESULTS

BPTS inhibited proliferation of MDA-MB-231 cells with an IC value of 10 μg/mL at 48 h. BPTS inhibited migration of MDA-MB-231 cells, and the western blot results demonstrated that BPTS reduced p-PI3K, p-Akt and p-mTOR protein expression levels in MDA-MB-231 cells. Additionally, the results were confirmed using a PI3K inhibitor and an mTOR inhibitor. BPTS decreased proliferation and migration of MDA-MB-231 cells possibly through inhibiting the PI3K/Akt/mTOR signaling pathway.

CONCLUSIONS

The results highlight the therapeutic potential of BPTS for treating patients with triple-negative breast cancer.

摘要

背景

本研究旨在探讨菝葜（Maxim.）Franquet（BP）活性化合物 BP 总皂苷（BPTS）对 MDA-MB-231 细胞的影响，并探讨 BPTS 介导的 PI3K/Akt/mTOR 通路衰减的潜在机制。

方法

在三个不同浓度下，考察 BPTS 对 MDA-MB-231 细胞的细胞毒性、凋亡诱导和迁移的影响。用 CCK-8 法、划痕愈合试验和流式细胞术来证明 BPTS 的作用。此外，用 Western blot 法检测 PI3K/Akt/mTOR 信号通路的主要成员的表达。为了验证潜在机制，使用了 PI3K 抑制剂和 mTOR 抑制剂。

结果

BPTS 在 48 小时时以 10μg/mL 的 IC 值抑制 MDA-MB-231 细胞的增殖。BPTS 抑制 MDA-MB-231 细胞的迁移，Western blot 结果表明，BPTS 降低了 MDA-MB-231 细胞中 p-PI3K、p-Akt 和 p-mTOR 蛋白的表达水平。此外，还使用了 PI3K 抑制剂和 mTOR 抑制剂来验证结果。BPTS 可能通过抑制 PI3K/Akt/mTOR 信号通路来降低 MDA-MB-231 细胞的增殖和迁移。