Department of Obstetrics and Gynecology, Faculty of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
Hum Cell. 2024 Sep;37(5):1462-1474. doi: 10.1007/s13577-024-01116-4. Epub 2024 Aug 8.
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.
对于治疗耐药性卵巢透明细胞癌，需要开发优于现有化疗治疗的新型疗法。我们研究了二甲双胍对卵巢透明细胞癌的抗肿瘤作用，及其与化疗联合使用的抗肿瘤作用增强效果，以及其分子调节机制。首先，我们使用水溶性四唑盐法评估了卵巢透明细胞癌细胞系的活力，发现二甲双胍抑制了细胞活力。顺铂和二甲双胍联合治疗可显著抑制细胞活力。相比之下，紫杉醇和二甲双胍联合治疗与无二甲双胍组相比，活力没有显著差异。Western blot 分析显示，一些细胞系中 AMP 激活的蛋白激酶磷酸化增加，而特定细胞系中哺乳动物雷帕霉素靶蛋白的磷酸化受到抑制。流式细胞术分析显示，二甲双胍处理组的细胞凋亡率显著增加，特定细胞系的细胞周期阻滞在 G2/M 期。这些结果表明，二甲双胍可能对培养的卵巢透明细胞癌细胞有效，特别是与顺铂联合使用时。
