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Article Publish Status: FREE
Abstract Title:

Astragaloside IV sensitizes non-small cell lung cancer cells to cisplatin by suppressing endoplasmic reticulum stress and autophagy.

Abstract Source:

J Thorac Dis. 2020 Jul ;12(7):3715-3724. PMID: 32802451

Abstract Author(s):

Song-Tao Lai, Yan Wang, Fei Peng

Article Affiliation:

Song-Tao Lai

Abstract:

Background: Cisplatin is an effective chemotherapeutic drug for treating various cancers including non-small cell lung cancer (NSCLC), but resistance to cisplatin remains the main limitation to its use in clinic. Astragaloside IV (AS-IV), which is derived from, has been proven to participate in various anti-cancer activities including anti-cancer, anti-oxidative, and anti-inflammatory functions.

Method: In this study, we explored the role of AS-IV in cisplatin chemoresistance to NSCLC cells by establishing cisplatin-resistant the NSCLC cell lines, A549and H1299.

Results: Cisplatin inhibited viability and promoted apoptosis of A549and H1299cells in a dose-dependent manner. In addition, cisplatin upregulated the levels of autophagy-related proteins (Beclin1, LC3 II/I) and endoplasmic reticulum (ER) stress-related proteins (glucose regulated protein 78: GRP78, protein kinase R (PKR)-like endoplasmic reticulum kinase: PERK), indicating that cisplatin caused autophagy and ER stress in NSCLC cells. However, treatment combined with AS-IV dose-dependently suppressed cell viability and increased the cell apoptosis rate in A549and H1299cells, suggesting that AS-IV elevated the anti-tumor role of cisplatin in NSCLC cells. AS-IV treatment suppressed the expression of GRP78 and Beclin1. Inhibition of ER stress or autophagy both counteracted the inhibitory effect of AS-IV on chemoresistance to cisplatin in NSCLC cells.

Conclusions: AS-IV sensitized NSCLC cells to cisplatin through suppressing ER stress and autophagy. This study provides a novel strategy of cisplatin combined with AS-IV for the treatment of cisplatin-resistant NSCLC patients.

Study Type : In Vitro Study

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Sayer Ji
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