Protective effects of liquiritin on polycystic ovary syndrome through modulating ovarian granulosa cell proliferation and apoptosis via miR-206/PI3K/AKT pathway.

Abstract

Polycystic ovarian syndrome (PCOS) is a frequent metabolic disorder in premenopausal woman, featured with increased androgen, reduced ovulation and insulin resistance. An increasing number of reports have confirmed that microRNAs (miRNAs) play pivotal roles in PCOS. However, the diagnostic mechanisms of microRNA (miR)-206 in PCOS remain unclear. Liquiritin, extracted from Glycyrrhiza Radix, has multiple pharmacological activities in diseases, including PCOS. Our report was designed to explore whether liquiritin play a role in PCOS by regulating human ovarian granulosa cell-like KGN cells proliferation and apoptosis through miR-206/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and to further elucidate the underlying molecular mechanisms. KGN cells were exposed to various concentration (0, 20, 40, 80μM) of liquiritin for 48h, cell proliferation and apoptosis were measured by 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide (MTT) and flow cytometry analysis. Reverse transcription‑quantitative polymerase chain reaction was conducted to checked the levels of miR-206 in KGN cells. The protein expression levels of cleaved caspase3, caspase3, phosphorylated (p)-AKT and AKT were analyzed using Western blot assay. We found that liquiritin stimulation led to reduced viability and enhanced apoptotic KGN cells, which along with increased cleaved caspase3 and cleaved caspase3/caspase3 ratio. Moreover, liquiritin obviously reduced p-AKT expression and p-AKT/AKT ratio. MiR-206 was up-regulated in liquiritin-treated KGN cells, however, all these results were reversed by miR-206 inhibitor. In conclusion, our findings suggested that liquiritin exerted anti-proliferative and apoptosis-inducing roles in KGN cells via miR-206/PI3K/AKT pathway, suggesting that liquiritin may be an effective therapeutic target for PCOS treatment.