Radix Tetrastigma Extracts Enhance the Chemosensitivity in Triple-Negative Breast Cancer Via Inhibiting PI3K/Akt/mTOR-Mediated Autophagy.

Abstract

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, up-regulated 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 MDA-MB-468 cells were induced and xenograft models were established. We found that RTEs inhibited autophagy of MDA-MB-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.

• Authors: Shuo Zhang, Tongxing Cui, Yin Duan, Hongchen Zhang, Bei Wang, Huiling Chen, Junjie Ni, Yilin Shen, Xiao-Ai Lv
• Journal: Clinical breast cancer (Clin Breast Cancer) Vol. 22 Issue 2 Pg. 89-97 (02 2022) ISSN: 1938-0666 [Electronic] United States
• PMID: 34535390 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Antioxidants
• Drugs, Chinese Herbal
• Plant Extracts
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Drugs, Chinese Herbal (pharmacology)
• Female
• Humans
• Mice
• Phytotherapy (methods)
• Plant Extracts (pharmacology)
• Plants, Medicinal (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Triple Negative Breast Neoplasms (drug therapy, pathology)