Protective effect of propofol via the regulation of ovarian granulosa cell proliferation and apoptosis

Propofol is an anesthetic frequently used in surgery. Accumulating evidence suggests that propofol exhibits an effect on cell viability, apoptosis and invasion in several types of cancer cells. MicroRNAs (miRNAs) have been reported to play pivotal roles in the development of polycystic ovary syndrome (PCOS). However, the diagnostic applications of miR-451a in PCOS remain unknown. The present study aimed to elucidate the effects of propofol on ovarian granulosa cell proliferation and apoptosis and illustrate the specific mechanisms associated with this process. Human ovarian granulosa cell-like KGN cells, which were used as a representative of granulosa cells in the present study, were treated with different concentrations (0, 1, 5 and 10 µg/ml) of propofol for 48 h and cell proliferation and apoptosis were assessed using MTT and flow cytometry assays, respectively. Propofol treatment resulted in significant inhibition of cell viability and induction of apoptosis in KGN cells, which was accompanied with increased cleaved caspase 3 and suppressed pro-caspase 3 expression levels. Furthermore, propofol reduced Wnt3a and β-catenin protein and mRNA expression levels. miR-451a expression in KGN cells was evaluated by reverse transcription-quantitative PCR (RT-qPCR). miR-451a expression was upregulated in propofol-stimulated KGN cells. The data further demonstrated that miR-451a mimics suppressed cell proliferation and increased apoptosis of KGN cells compared with cells transfected with control mimics. Furthermore, the association between miR-451a and propofol was investigated. Rescue experiments were performed to investigate the anti-proliferative mechanism of propofol in ovarian granulosa cells. KGN cells were transfected with miR-451a inhibitor or inhibitor control sequences for 6 h and treated with 10 µg/ml propofol for an additional 48 h. The results from the MTT, RT-qPCR and western blot assays indicated that 10 µg/ml propofol inhibited cell viability, induced apoptosis, enhanced cleaved caspase 3 expression, reduced pro-caspase 3 levels and inhibited the protein and mRNA expression of Wnt3a and β-catenin. However, inhibition of miR-451a demonstrated the opposite effects. In conclusion, the results of the present study revealed that propofol exerted an anti-proliferative and apoptosis-inducing role in ovarian granulosa cells through mediation of miR-451a expression. In addition, the data indicated that miR-451a may be used as an effective therapeutic target for PCOS treatment.