Nan Li, Liang Yang, Xinna Deng, Yanan Sun

Ovarian cancer is one of the most fatal gynecologic malignancies, with most patients diagnosed at the late stage due to insidious onset and lack of early onset specific symptoms. Previous studies have implied that isoliquiritigenin (ILQ) is a promising chemopreventive agent against oral cancer. This study aimed to investigate effects of ILQ and elucidate the related mechanism. Ovarian cancer cell lines, SKOV3 and OVCAR3, were treated with various concentrations of ILQ to detect the dose-dependent effects of ILQ and select the suitable concentration. CCK8 assay and clone formation efficiency assays were used to detect viability and proliferation. The cell migration, invasion, and apoptosis were evaluated by wound healing assays, transwell, and flow cytometry assays. The expression of apoptosis-related proteins (Caspase-3, Caspase3-p17, Bcl-2, Bax, and Bim) and related-signaling pathway proteins were also detected by Western blot. It was observed that the treatment of ILQ inhibited the survival and proliferation of SKOV3 and OVCAR3 cells. ILQ treatment inhibited migration and invasion, and induced apoptosis in SKOV3 and OVCAR3 cells. Also, the ILQ treatment increased the Bax/Bcl-2 ratio in SKOV3 and OVCAR3 cells, suggesting that a mitochondrial apoptotic pathway was triggered. It was also observed that, after treated with ILQ, the phosphorylated form of Akt and mTOR decreased and the expression of GSK3β increased, while P70/S6K decreased. ILQ treatment also decreased the expression of Wnt3a and, therefore, caused the decrease of phosphorylated ERK. ILQ also suppressed the PI3K/Akt/mTOR pathway by reduced the expression level of p-Akt, p-mTOR, P70/S6K and Cyclin D1 in Ishikawa and ES-2 cells. The data suggested that ILQ inhibited viability, proliferation, and invasion, and induced apoptosis of SKOV3 and OVCAR3 cells through the PI3K/Akt/mTOR pathway. Together, the data revealed that ILQ treatment may be used as a novel strategy for ovarian cancer therapy.