Oleanolic acid alleviates ovarian cancer by regulating the miR-122/PDK4 axis to induce autophagy and inhibit glycolysis in vivo and in vitro.

BACKGROUND: Ovarian cancer (OC) is a gynecological tumor with a high incidence and poor prognosis. Oleanolic acid (OA) plays a crucial role in cancers with its anti-cancer function. The study aimed to identify the effects of OA on OC development in vivo and in vitro. METHODS: The cell viability, migration, and invasion were analyzed by the CCK-8 approach and the Transwell assay. The glycolysis was evaluated by the glucose uptake rate, lactate content, and glycolysis-related protein expression. The autophagy was analyzed by determining autophagy-related protein expression. The tumor volume and weight were measured. The H&E and immunohistochemical staining were performed to determine pathological injuries and Ki67 expression of the tumor tissue. The levels of miR-122 and PDK4 were measured by qRT-PCR. RESULTS: OA inhibited the cell viability, migration, invasion, and glycolysis, and induced the autophagy of OC cells in a dose-dependent manner. Moreover, miR-122 was down-regulated in OC cells and increased by OA. Knocking down miR-122 effectively reversed the effects of OA on OC cells. PDK4 was clarified as a miR-122 target. Moreover, OA suppressed tumor volume and weight and Ki67 expression but induced pathological injuries of in tumor tissue. In vivo and in vitro, the overexpression of PDK4 and miR-122 effectively abolished the effects of OA and the overexpression of PDK4 on OC cells and tumor tissue, respectively. CONCLUSIONS: In conclusion, OA induced autophagy and inhibited glycolysis to attenuate OC progression by regulating the miR-122/PDK4 axis, providing a theoretical basis for clinical treatment of OC with OA, and novel therapeutic targets of OC.