Title:Astragaloside IV Overcomes Anlotinib Resistance in Non-small Cell Lung
Cancer through miR-181a-3p/UPR-ERAD Axis
Volume: 21
Issue: 4
Author(s): Lihuai Wang, Tonglin Sun, Xiao Yang, Zhi Wen, Yinhui Sun*Hua Liu*
Affiliation:
- Department of Pathophysiology, Medical College, Hunan University of Traditional
Chinese Medicine, Changsha, 410208, Hunan Province, China
- Department of Oncology, the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha,
410000, Hunan Province, China
Keywords:
Astragaloside IV, non-small cell lung cancer, anlotinib, miR-181a-3p, UPR, ERAD.
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.