Quercetin radiosensitizes non-small cell lung cancer cells through the regulation of miR-16-5p/WEE1 axis

IUBMB Life. 2020 May;72(5):1012-1022. doi: 10.1002/iub.2242. Epub 2020 Feb 6.

Abstract

Background: Quercetin, a widely distributed bioflavonoid, plays a role in combating diverse human cancers including non-small cell lung cancer (NSCLC). However, the role of quercetin in reversing the radioresistance of NSCLC cells and its underlying mechanism are far from being elucidated.

Method: Radiation-resistant NSCLC cell lines were established. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of miR-16-5p and WEE1 G2 checkpoint kinase (WEE1) mRNA in radiation-resistant cells. After being treated with different concentrations of quercetin and different doses of X-ray, cell proliferation and apoptosis were monitored by CCK-8 assay, colony formation assay, and flow cytometry, respectively. Ultimately, the targeting relationship between miR-16-5p and WEE1 was verified via a dual fluorescent reporter gene assay.

Results: The expression of miR-16-5p was down-regulated in radiation-resistant cells, while the expression of WEE1 was up-regulated. Quercetin enhanced the radiosensitivity of NSCLC cells in a dose- and time-dependent manner. Furthermore, quercetin treatment increased the expression of miR-16-5p and decreased the expression of WEE1. The function of quercetin was reversed by miR-16-5p inhibitors or the transfection of WEE1 overexpressing plasmids.

Conclusion: In conclusion, quercetin enhanced the radiosensitivity of NSCLC cells via modulating the expression of miR-16-5p and WEE1.

Keywords: NSCLC; WEE1; miR-16-5p; quercetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Proliferation / radiation effects
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lung Neoplasms / radiotherapy
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Models, Biological
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Quercetin / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radiation Tolerance / drug effects*
  • Radiation Tolerance / genetics
  • Radiation-Sensitizing Agents / pharmacology*
  • Signal Transduction
  • X-Rays

Substances

  • Antagomirs
  • Cell Cycle Proteins
  • MIRN16 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Radiation-Sensitizing Agents
  • Quercetin
  • Luciferases
  • Protein-Tyrosine Kinases
  • WEE1 protein, human