Radix Tetrastigma Extracts Enhance the Chemosensitivity in Triple-Negative Breast Cancer Via Inhibiting PI3K/Akt/mTOR-Mediated Autophagy
Radix Tetrastigma Extracts Enhance the Chemosensitivity in Triple-Negative Breast Cancer Via Inhibiting PI3K/Akt/mTOR-Mediated Autophagy
复制标题
四柱提取物通过抑制 PI3K/Akt/mTOR 介导的自噬增强三阴性乳腺癌的化疗敏感性
DOI：
10.1016/j.clbc.2021.07.015
复制
发表时间：
2022
影响因子：
3.1
通讯作者：
Xiao-ai Lv
中科院分区：
文献类型：
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作者：
Shuo Zhang;Tongxing Cui;Yin Duan;Hongchen Zhang;Bei Wang;Huiling Chen;Junjie Ni;Yilin Shen;Xiao-ai Lv
目的：肿瘤耐药是导致化疗失败的主要因素之一。本研究旨在探讨三叶青提取物（RTEs）对紫杉醇诱导的三阴性乳腺癌（TNBC）细胞自噬及化疗敏感性的影响。方法：诱导MDA-MB-468/Taxol耐药细胞株，并用RTEs和/或Taxol处理。用MDA-MB-468/Taxol.细胞皮下接种小鼠以建立异种移植模型。通过蛋白质印迹法测量相关蛋白质水平。采用流式细胞术、CCK-8和EdU法分别检测细胞凋亡、细胞活力和细胞增殖。结果如下：在MDA-MB-468/Taxol细胞中，RTEs和Taxol处理增加了细胞凋亡，降低了细胞活力和增殖，上调了抗自噬标志物LC3I/LC3II比率，并增强了mTOR水平。通过RTEs和Taxol处理，mTOR沉默下调LC 3I/LC 3II比率，增加细胞活力和增殖，并减少细胞凋亡，而mTOR过表达显示相反的结果。PI3K抑制剂降低AKT和mTOR水平，对细胞活性的影响与mTOR沉默的结果相似，RTEs和Taxol注射后，移植瘤变小，AKT、mTOR、LC3I/LC3II比值和凋亡标志物calyzed caspase-3升高。结论：RTEs通过抑制PI3K/Akt/mTOR介导的自噬增强TNBC耐药细胞对紫杉醇的化疗敏感性，Micro：RTEs在多种肿瘤中发挥抗肿瘤作用，本研究确定了其在TNBC中的作用。诱导耐药MDAMB-468细胞，建立异种移植瘤模型。我们发现，RTEs抑制MDAMB-468/Taxol细胞的自噬并减少肿瘤生长。抑制PI3K/Akt/mTOR通路促进MDA-MB-.468/Taxol细胞的自噬。我们可能为TNBC的治疗提供一种新的潜在策略。
Objective: Drug resistance in tumors is one of the major factors that leads to chemotherapy failure. This study aims to.investigate the effect of Radix Tetrastigma extracts (RTEs) on Taxol-induced autophagy and the chemosensitivity against.drug resistance in triple-negative breast cancer (TNBC). Methods: Taxol-resistant MDA-MB-468 (MDA-MB-468/Taxol).cells were induced and treated with RTEs and/or Taxol. Mice were subcutaneously inoculated with MDA-MB- 468/Taxol.cells to establish xenograft models. The associated protein levels were measured by western blotting. Flow cytometry,.CCK-8 and EdU assay were performed to detect cell apoptosis, viability, and proliferation, respectively. Results: In.MDA-MB-468/Taxol cells, RTEs & Taxol treatment increased cell apoptosis, reduced cell viability and proliferation, upregulated anti-autophagy marker LC3I/LC3II ratio, and enhanced mTOR level. With RTEs & Taxol treatment, mTOR.silencing downregulated LC3I/LC3II ratio, increased cell viability and proliferation, and reduced cell apoptosis, while.mTOR overexpression showed the opposite results. PI3K inhibitor reduced AKT and mTOR levels, and the effects on.cell activities were similar to the results of mTOR silencing.After RTEs & Taxol injection, xenograft tumor was smaller, and.AKT, mTOR, LC3I/LC3II ratio and apoptotic marker cleaved caspase-3 were increased. Conclusion: RTEs enhanced.the chemosensitivity of resistant TNBC cells to Taxol through inhibiting PI3K/Akt/mTOR-mediated autophagy.Micro:.RTEs exerted anti-tumor effects in various cancers, and this study determined its role in TNBC. Taxol-resistant MDAMB-468 cells were induced and xenograft models were established. We found that RTEs inhibited autophagy of MDAMB-468/Taxol cells and reduced tumor growth. Inhibition of PI3K/Akt/mTOR pathway promoted autophagy of MDA-MB-.468/Taxol cells. We may provide a new potential strategy for TNBC treatment.