Thioridazine induces pyrolysis and autophagy in epithelial ovarian cancer
Thioridazine exhibits inhibitory effects on various tumors, including epithelial ovarian cancer, but the mechanisms remain unclear. Proliferation and invasion were assessed using CCK8 and Matrigel invasion assays. Autophagy and pyroptosis-related markers were detected via Western blot. Autophagy flux was tracked using the mRFP-GFP-LC3 reporter. Autophagy inhibitors 3MA andBufA1 were used to confirm whether autophagy flux was functioning properly. RNA sequencing was performed to identify differentially expressed genes, and Co-IP was used to detect interacting proteins. A subcutaneous tumorigenesis experiment in nude mice was conducted to evaluate the effect of thioridazine in vivo. As a result, thioridazine inhibited proliferation and invasion of EOC while promoting autophagy and pyroptosis. The upregulation of the pyroptosis marker NLRP3 may be attributed to DRD2 inhibition. Inhibition of autophagy enhanced NLRP3 expression, and the autophagy inhibitor CQ increased the tumor-inhibiting effects of thioridazine. In conclusion, thioridazine inhibited EOC proliferation and invasion by inducing pyroptosis and autophagy, with autophagy playing a protective role in thioridazine treatment. Thioridazine combined with the autophagy inhibitor CQ may be an effective treatment for EOC. Overall design: After being treated with 15µM thioridazine for 24h, the SKOV3 cells were lysed with Trizol and collected for RNA sequencing.