Resveratrol augments paclitaxel sensitivity by modulating miR-671-5p/STOML2/PINK1/Parkin-mediated autophagy signaling in A549 cell

J Biochem Mol Toxicol. 2024 Jan;38(1):e23557. doi: 10.1002/jbt.23557. Epub 2023 Oct 16.

Abstract

Paclitaxel (PTX) resistance has become a notable clinical concern of Non-small cell lung cancer (NSCLC). Our study aim is to investigate the effects of Resveratrol (RES) on NSCLC cells that have developed resistance to PTX. The NSCLC cell line A549 was employed in this investigation to establish a PTX-resistant NSCLC cell line, denoted as A549/PTX, and established tumor transplantaton model. The presence of miR-671-5p, Stomatin-like protein 2 (STOML2), and mitophagy biomarkers was evaluated using quantitative teal-time PCR (qRT-PCR) and western blot, The assessment of cell proliferation and apoptosis was conducted through the utilisation of colony formation and flow cytometry assays. The investigation of mitochondrial autolysosomes was conducted using transmission electron microscopy (TEM). Our results showed that the application of RES therapy resulted in a substantial improvement in the sansitivity of A549/PTX cells. RES exhibited an augmentation of apoptosis and a suppression of mitophagy in A549/PTX cells. RES induced an upregulation in the expression of miR-671-5p. This, in turn, leaded to the inhibition of STOML2, a protein that directly interacts with PINK1. In summary, our research indicates that RES improved the susceptibility of A549/PTX cells to PTX through miR-671-5p-mediated STOML2 inhibition.

Keywords: NSCLC; PINK1/Parkin; Resveratrol; STOML2; miR-671-5p.

MeSH terms

  • A549 Cells
  • Apoptosis
  • Autophagy
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Humans
  • Lung Neoplasms* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Paclitaxel / pharmacology
  • Protein Kinases
  • Resveratrol / pharmacology
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Paclitaxel
  • Resveratrol
  • MicroRNAs
  • Ubiquitin-Protein Ligases
  • Protein Kinases
  • MIRN671 microRNA, human