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.