Department of Histology and Embryology, Faculty of Medicine, Muğla Sıtkı Koçman University, Muğla, Türkiye;
Rom J Morphol Embryol. 2023 Jul-Sep;64(3):355-361. doi: 10.47162/RJME.64.3.07.
Today, many anticancer drugs are used clinically for ovarian cancer, one of the leading causes of cancer-related deaths in women. Phenformin is an antidiabetic drug of the biguanide class. It improves the antiproliferative activity in cancer cells. Hypoxia is an important component associated with ovarian cancer and its tumor microenvironment. The aim of this study was to investigate the anticancer effects of Phenformin in SKOV-3 human ovarian cancer cells under hypoxic conditions. SKOV-3 human ovarian cancer cells treated with different doses of Phenformin (0.5 mM, 1 mM, 2 mM, 5 mM) for 24 hours were subjected to WST-1 cell viability assay and Annexin V apoptosis assay. A dose-dependent decrease in cell viability with Phenformin treatment was observed. In addition, Phenformin activated percentage of apoptotic SKOV-3 cancer cells in a dose-dependent manner. In this study, Cobalt(II) chloride (CoCl2) treatment leads to increased hypoxia-inducible factor-1alpha (HIF-1α) expression and Phenformin can recover hypoxic condition. HIF-1α protein expression was significantly correlated with cell viability assay and apoptosis assay. We also found that Phenformin inhibits expression of phosphoinositide-dependent kinase 1 (PDK1) in SKOV-3 ovarian cancer cells. The ability to migrate to cancer cells was significantly reduced in a dose-dependent manner with Phenformin. This data demonstrates that Phenformin treatment can induce apoptosis and inhibit proliferation in ovarian cancer cells under hypoxic conditions. The findings reveal that HIF-1α is a new target for the treatment of ovarian cancer.
如今，许多抗癌药物被临床用于治疗卵巢癌，卵巢癌是导致女性癌症相关死亡的主要原因之一。苯乙双胍是一种双胍类抗糖尿病药物。它能提高癌细胞的抗增殖活性。缺氧是与卵巢癌及其肿瘤微环境相关的重要组成部分。本研究旨在研究苯乙双胍在缺氧条件下对 SKOV-3 人卵巢癌细胞的抗癌作用。用不同剂量的苯乙双胍（0.5mM、1mM、2mM、5mM）处理 SKOV-3 人卵巢癌细胞 24 小时后，进行 WST-1 细胞活力测定和 Annexin V 凋亡测定。结果显示，苯乙双胍处理后细胞活力呈剂量依赖性下降。此外，苯乙双胍以剂量依赖性方式激活 SKOV-3 癌细胞的凋亡百分比。在这项研究中，氯化钴（CoCl2）处理导致缺氧诱导因子-1α（HIF-1α）表达增加，而苯乙双胍可以恢复缺氧状态。HIF-1α 蛋白表达与细胞活力测定和凋亡测定显著相关。我们还发现，苯乙双胍抑制 SKOV-3 卵巢癌细胞中磷酸肌醇依赖性激酶 1（PDK1）的表达。苯乙双胍以剂量依赖性方式显著降低癌细胞的迁移能力。这些数据表明，苯乙双胍处理可以在缺氧条件下诱导卵巢癌细胞凋亡和抑制增殖。研究结果表明，HIF-1α 是治疗卵巢癌的一个新靶点。
