Ovarian cancer is the most malignant
gynecologic neoplasm in women and has the worst prognosis of all
cancer types in women based on the 5-year survival rates. A previous study indicated that
mangiferin exerts an anti-neoplastic effect on human
ovarian cancer cells by targeting Notch3. Additionally, it has been demonstrated that Notch signaling is a functionally important downstream effector of Yes-associated
protein (YAP), therefore it was hypothesized that YAP may be involved in the antitumor effect of
mangiferin. The present study aimed to further reveal the
mangiferin-mediated inhibitory effect on
ovarian cancer and investigate the molecular anticancer mechanism of
mangiferin. Based on the in vitro data, accompanied with the significantly reduced cell proliferation of
mangiferin-treated cells compared with
mangiferin-treated YAP-overexpressed cells (P<0.05), YAP expression was identified to be substantially downregulated by
mangiferin. In contrast, observations of the cell morphology and apoptotic percentages revealed that the antitumor effect of
mangiferin may be reversed by YAP overexpression. Furthermore, decreased levels of migration and invasion were observed in
mangiferin-treated cells, which may also be abrogated by YAP overexpression. Thus, these data further demonstrated that
mangiferin inhibits
metastasis by regulating YAP. Additionally, due to the frequent chemoresistance observed in
cisplatin-based
chemotherapy, the present study evaluated the
cisplatin resistance in OVCAR8 cells and elucidated that
mangiferin may sensitize the
tumor cells to
cisplatin; and this improved sensitization was also abolished by YAP overexpression. These results collectively indicated that YAP was not only closely associated with the anticancer effect of
mangiferin, but also mediated drug resistance in
tumor. Furthermore, the downregulation of downstream
TEA domain transcription factor 4 expression was observed in the
mangiferin-treated cells, further validating the inhibitory effect of
mangiferin on YAP. In addition, OVCAR8 cell xenograft models revealed that through increasing the sensitivity of a
tumor to
cisplatin,
mangiferin inhibited the growth of a
tumor and increased the survival time of
tumor xenograft mice. Based on these results, it was concluded that
mangiferin may inhibit
tumor cell growth and enhance
cisplatin-sensitivity in OVCAR8 cells via the regulation of the YAP pathway. Altogether, by targeting YAP and enhancing the response to
cisplatin treatment,
mangiferin potentially functioned as a novel therapeutic agent in the treatment of
ovarian cancer.