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.
Keywords
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Article info
Publication history
Published online: August 04, 2021
Accepted:
July 29,
2021
Received in revised form:
July 13,
2021
Received:
March 29,
2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
