Synergistic effect of Tripterygium glycosides and cisplatin on drug-resistant human epithelial ovarian cancer via ILK/GSK3β/Slug signal pathway

The side-effects of therapeutic drugs and the intrinsic or acquired cisplation resistance are considered impediments in the clinic treatment of human epithelial ovarian cancer, which contribute heavily to the startlingly high mortality. It is imperative to look for drugs to inhibit cancer and minimize the chemotherapy resistance safely and effectively from the Chinese herbal medicine. In the present study, we evaluated the anti-cancer effect of Tripterygium glycosides (GTW) and its sensitizing effect with cisplation (DDP) both in vitro and in vivo. The 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay, transwell assay, and scratch wound healing assay demonstrated that GTW and DDP+GTW prominently inhibited the proliferation, migration, and invasion of SKOV3/DDP cells. In addition, treatment using GTW and DDP+GTW for 24 h significantly decreased the expression of ILK, p-AKT, p-GSK3β, N-Cadherin, and Slug, and markedly enhanced the expression of E-cadherin. Moreover, animal results confirmed that GTW and DDP+GTW significantly inhibited the tumor volume, increased the apoptosis of tumors cells and reduced the production of tumor markers CA125 and HE4 in mice serum. Similar to the results in vitro, GTW and DDP+GTW significantly inhibited the expression of proteins in epithelial-mesenchymal transition (EMT) and ILK/GSK3β/Slug signal pathway in tumors in vivo. In conclusion, our results indicated that GTW may be served as a potential therapeutic drug combination with DDP to treat drug resistant ovarian cancer via regulating ILK/GSK3β/Slug signal pathway.