PDF(Pubmed)
Abstract：
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.
摘要：
今天,许多抗癌药物在临床上用于卵巢癌，女性癌症相关死亡的主要原因之一。苯乙双胍是双胍类的抗糖尿病药物。它提高了癌细胞的抗增殖活性。缺氧是卵巢癌及其肿瘤微环境的重要组成部分。本研究的目的是研究苯乙双胍在低氧条件下对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,对5mM)24小时进行WST-1细胞活力测定和膜联蛋白V凋亡测定。观察到用苯乙双胍处理的细胞活力的剂量依赖性降低。此外,苯乙双胍以剂量依赖性方式激活凋亡SKOV-3癌细胞的百分比。在这项研究中,氯化钴（II）（CoCl2）处理导致低氧诱导因子-1α（HIF-1α）表达增加，苯乙双胍可以恢复低氧状态。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迁移至癌细胞的能力。该数据表明,苯乙双胍处理可在缺氧条件下诱导卵巢癌细胞凋亡并抑制增殖。提示HIF-1α是卵巢癌治疗的新靶点。
