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Assessing the antitumor effects of metformin on ovarian clear cell carcinoma
Satoshi Takemori1, Tohru Morisada2, Makoto Osaka1
1Department of Obstetrics and Gynecology, Faculty of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
Abstract:
Developing novel therapies that outperform the existing chemotherapeutic treatments is required for treatment-resistant ovarian clear cell carcinoma. We investigated the antitumor effect of metformin on ovarian clear cell carcinoma, enhancement of the antitumor effect by its combination with chemotherapy, and its molecular regulatory mechanism. First, we evaluated the viability of ovarian clear cell carcinoma lines using the water-soluble tetrazolium-1 assay and found that metformin suppressed cell viability. Cell viability was significantly suppressed by co-treatment with cisplatin and metformin. In contrast, co-treatment with paclitaxel and metformin showed no significant difference in viability compared with the group without metformin. Western blot analysis showed increased phosphorylation of AMP-activated protein kinase in some cell lines and suppressed phosphorylation of the mammalian target of rapamycin in a particular cell line. Flow cytometry analysis revealed a significant increase in the rate of apoptosis in the metformin-treated group and rate of cell cycle arrest at the G2/M phase in a particular cell line. These results indicated that metformin may be effective against cultured ovarian clear cell carcinoma cells, particularly in combination with cisplatin.
Insights
Metformin shows promise in treating ovarian clear cell carcinoma by suppressing cancer cell viability. Its combination with cisplatin significantly enhances this antitumor effect, offering a potential new therapeutic strategy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Treatment-resistant ovarian clear cell carcinoma necessitates novel therapeutic strategies.
- Existing chemotherapies have limitations in efficacy against this specific cancer type.
Purpose of the Study:
- To investigate the antitumor effects of metformin on ovarian clear cell carcinoma.
- To evaluate the synergistic potential of metformin combined with chemotherapy (cisplatin and paclitaxel).
- To elucidate the molecular mechanisms underlying metformin's action.
Main Methods:
- Cell viability was assessed using the water-soluble tetrazolium-1 assay.
- Western blot analysis was employed to examine protein phosphorylation (AMPK, mTOR).
- Flow cytometry was used to analyze apoptosis rates and cell cycle progression.
Main Results:
- Metformin alone suppressed ovarian clear cell carcinoma cell viability.
- Combination therapy with cisplatin and metformin significantly enhanced the suppression of cell viability.
- Metformin treatment led to increased apoptosis and G2/M phase cell cycle arrest.
- Molecular analysis indicated modulation of AMPK and mTOR pathways.
Conclusions:
- Metformin exhibits significant antitumor activity against ovarian clear cell carcinoma cells in vitro.
- Combining metformin with cisplatin demonstrates a potent synergistic effect, suggesting clinical potential.
- Metformin's mechanism involves inducing apoptosis and cell cycle arrest, potentially via AMPK/mTOR pathway regulation.
