Abstract
Ovarian cancer is one of the leading causes of death in gynecological malignancies, and the resistance to chemotherapeutic agents remains a major challenge to successful ovarian cancer chemotherapy. Dihydromyricetin (DHM), a natural flavonoid derived from Ampeopsis Grossdentata, has been widely applied in food industry and medicine for a long time. However, little is known about the effects of DHM on ovarian cancer and the underlying mechanisms. In this study, we demonstrated that DHM could effectively inhibit the proliferation of ovarian cancer cells and induce cell apoptosis. Survivin, an inhibitor of apoptosis (IAPs) family member, exhibited a decreased expression level after DHM treatment, which may be attributed to the activation of p53. Moreover, DHM markedly sensitized paclitaxel (PTX) and doxorubicin (DOX) resistant ovarian cancer cells to PTX and DOX by inhibiting survivin expression. Collectively, our findings highlight a previously undiscovered effect of DHM, which induces apoptosis and reverses multi-drug resistance against ovarian cancer cells through downregulation of survivin.
Highlights
Ovarian cancer is one of the most lethal gynecological malignancies in the USA and an estimated 14,180 deaths are expected in 20151
The in vitro anti-proliferation effect of DHM was assessed in A2780 and SKOV3 ovarian cancer cells and IOSE80 human ovarian epithelial cells
Previous studies have revealed the effects of DHM on cell proliferation, colony formation, cell cycle distribution and cell apoptosis in a plethora of cancer cell lines, such as hepatocellular carcinoma, osteosarcoma, and melanoma cells[31,33,34]
Summary
Ovarian cancer is one of the most lethal gynecological malignancies in the USA and an estimated 14,180 deaths are expected in 20151. As many as 70% of ovarian cancer patients would develop advanced-staged disease and resistance to treatment, depriving long-term benefit from treatment[5]. This observation highlights the importance of better understanding the mechanism of therapy and devising more effective strategies to conquer therapeutic resistance. Upregulation of inhibitors of apoptosis proteins (IAPs) expression has been associated with drug resistance in various cancers[6]. Survivin is a potential molecular target in cancer therapy because of its important roles in inhibiting apoptosis, enhancing proliferation and promoting angiogenesis. The effects of DHM combined with chemotherapeutic agents against resistant ovarian cancer cells were evaluated
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