State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
Sci Rep. 2017 Apr 24;7:46060. doi: 10.1038/srep46060.
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.
卵巢癌是妇科恶性肿瘤导致死亡的主要原因之一，而对化疗药物的耐药性仍是卵巢癌化疗成功的主要挑战。二氢杨梅素（DHM）是一种从藤茶中提取的天然黄酮类化合物，长期以来广泛应用于食品工业和医药领域。然而，关于 DHM 对卵巢癌的影响及其潜在机制知之甚少。在这项研究中，我们证明 DHM 可以有效抑制卵巢癌细胞的增殖并诱导细胞凋亡。凋亡抑制蛋白（IAPs）家族成员 survivin 在 DHM 处理后表达水平降低，这可能归因于 p53 的激活。此外，DHM 通过抑制 survivin 的表达，显著增强了紫杉醇（PTX）和多柔比星（DOX）耐药卵巢癌细胞对 PTX 和 DOX 的敏感性。总之，我们的研究结果揭示了 DHM 的一个先前未被发现的作用，即通过下调 survivin 诱导细胞凋亡并逆转卵巢癌细胞的多药耐药性。
