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

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Purpose: Resveratrol (REV), a natural compound found in red wine, exhibits antitumor activity in various cancers, includingovarian cancer (OC). However, its potential anti-tumor mechanisms in OC are not well characterized. Here, we tried to elucidatethe 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 wasmeasured using an Annexin V-FITC/PI apoptosis detection kit. The anti-metastasis effects of REV were evaluated by invasion assayand 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 andmigration of OV-90 and SKOV-3 cells. miR-34a was selected for further study due to its tumor suppressive roles in various humancancers. We found miR-34a overexpression enhanced the inhibitory effects of REV on OC cells, whereas miR-34a inhibition hadthe 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-2significantly 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.

Abstract

Purpose: Resveratrol (REV), a natural compound found in red wine, exhibits antitumor activity in various cancers, includingovarian cancer (OC). However, its potential anti-tumor mechanisms in OC are not well characterized. Here, we tried to elucidatethe 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 wasmeasured using an Annexin V-FITC/PI apoptosis detection kit. The anti-metastasis effects of REV were evaluated by invasion assayand 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 andmigration of OV-90 and SKOV-3 cells. miR-34a was selected for further study due to its tumor suppressive roles in various humancancers. We found miR-34a overexpression enhanced the inhibitory effects of REV on OC cells, whereas miR-34a inhibition hadthe 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-2significantly 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.

참고문헌 (47)

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