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Current Computer-Aided Drug Design

Editor-in-Chief

ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

Astragaloside IV Overcomes Anlotinib Resistance in Non-small Cell Lung Cancer through miR-181a-3p/UPR-ERAD Axis

Author(s): Lihuai Wang, Tonglin Sun, Xiao Yang, Zhi Wen, Yinhui Sun* and Hua Liu*

Volume 21, Issue 4, 2025

Published on: 17 January, 2024

Page: [441 - 451] Pages: 11

DOI: 10.2174/0115734099252873231117072107

Price: $65

Abstract

Background: Astragaloside IV (AS-IV) has been shown to have a curative effect on non-small cell lung cancer (NSCLC). This study aimed to elucidate the role of AS-IV in NSCLC cell anlotinib resistance (AR).

Methods: The NSCLC/AR cells, resistant to anlotinib, have been produced. The role of AS-IV in the AR of NSCLC cells about the miR-181a-3p/unfolded protein response (UPR)- endoplasmic reticulum associated degradation (ERAD) pathway was then discussed by treating the cells with anlotinib or AS-IV, or by manipulating them with inhibitors or mimics of miR- 181a-3p, HRD1 or Derlin-1 overexpression plasmids.

Results: We found that AS-IV could suppress the AR of NSCLC cells. In addition, miR-181a- 3p was elevated in NSCLC/AR cells. Functionally, AS-IV limited the AR of NSCLC cells by reducing miR-181a-3p. Further, activation of the UPR-ERAD pathway was correlated with AR in NSCLC cells. Increased sensitivity of NSCLC cells to anlotinib caused by miR-181a-3p inhibitor could be reversed by overexpression of HRD1 or Derlin-1.

Conclusion: This research revealed a promising NSCLC/AR treatment approach by showing that AS-IV exposed NSCLC cells to anlotinib by inhibiting the miR-181a-3p/UPR-ERAD axis.

Keywords: Astragaloside IV, non-small cell lung cancer, anlotinib, miR-181a-3p, UPR, ERAD.


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