Upregulation of MicroRNA-34a Sensitizes Ovarian Cancer Cells to Resveratrol by Targeting Bcl-2

Yonsei Med J. 2021 Aug;62(8):691-701. doi: 10.3349/ymj.2021.62.8.691.

Abstract

Purpose: Resveratrol (REV), a natural compound found in red wine, exhibits antitumor activity in various cancers, including ovarian cancer (OC). However, its potential anti-tumor mechanisms in OC are not well characterized. Here, we tried to elucidate the underlying mechanisms of REV in OC cells.

Materials and methods: The anti-proliferative effects of REV against OC cells were measured using CCK-8 assay. Apoptosis was measured using an Annexin V-FITC/PI apoptosis detection kit. The anti-metastasis effects of REV were evaluated by invasion assay and wound healing assay. The miRNA profiles in REV-treated cells were determined by microarray assay.

Results: Our results showed that REV treatment suppresses the proliferation, induces the apoptosis, and inhibits the invasion and migration of OV-90 and SKOV-3 cells. miR-34a was selected for further study due to its tumor suppressive roles in various human cancers. We found miR-34a overexpression enhanced the inhibitory effects of REV on OC cells, whereas miR-34a inhibition had the opposite effect in OC cells. In addition, we verified that BCL2, an anti-apoptotic gene, was found directly targeted by miR-34a. We also found that REV reduced the expression of Bcl-2 in OC cells. Further investigations revealed that overexpression of Bcl-2 significantly abolished the anti-tumor effects of REV on OC cells.

Conclusion: Overall, these results demonstrated that REV exerts anti-cancer effects on OC cells through an miR-34a/Bcl-2 axis, highlighting the therapeutic potential of REV for treatment of OC.

Keywords: Bcl-2; Resveratrol; microRNA-34a; ovarian cancer.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Resveratrol / pharmacology
  • Up-Regulation

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Resveratrol