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Upregulation of MicroRNA-34a Sensitizes Ovarian Cancer Cells to Resveratrol by Targeting Bcl-2
Shangli Yao1, Ming Gao1, Zujun Wang2
1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
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.
Insights
Resveratrol (REV) fights ovarian cancer (OC) by boosting miR-34a and reducing Bcl-2, a key mechanism for its anti-tumor effects. This highlights REV
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Resveratrol (REV), a natural compound from red wine, shows promise against various cancers.
- Its specific anti-tumor mechanisms in ovarian cancer (OC) require further elucidation.
Purpose of the Study:
- To investigate the anti-tumor mechanisms of Resveratrol (REV) in ovarian cancer (OC) cells.
- To explore the role of microRNA-34a (miR-34a) and Bcl-2 in REV's anti-cancer effects.
Main Methods:
- CCK-8 assay for proliferation.
- Annexin V-FITC/PI staining for apoptosis.
- Invasion and wound healing assays for metastasis.
- Microarray analysis for miRNA profiling.
Main Results:
- REV suppressed proliferation, induced apoptosis, and inhibited invasion/migration in OC cells.
- miR-34a overexpression enhanced REV's effects; miR-34a inhibition reversed them.
- miR-34a directly targets the anti-apoptotic gene BCL2.
- REV reduced Bcl-2 expression, and Bcl-2 overexpression counteracted REV's anti-tumor effects.
Conclusions:
- REV exerts anti-cancer effects on OC cells via an miR-34a/Bcl-2 signaling axis.
- This pathway highlights the therapeutic potential of REV for ovarian cancer treatment.
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