Anti-ovarian Cancer Effects Of CDDO-Me And Its Mechanisms

Ovarian cancer is one of the three female reproduction malignant cancers, though diagnostic level and chemotherapy raised a lot, 70% diagnosed ovarian cancer patients were found metastasis, which results in high death ratio. Therefore, finding novel targets and effective drugs has a long way to go. In ovarian cancer, many tumor surppressor gene p53, PTEN, RB1 and BRCA1 are either mutant or dysregulated. These proteins are all downstream proteins of deubiquitinase USP7, yet USP7's role in ovarian cancer is still unclear. CDDO-Me is a clinic III potent drug in treating type II Chronic diabetic nephropathy, and could effectively inhibit kinds of tumors. Previously, many proteins have been reported to be targets of CDDO-Me, but it cannot thoroughly explain clinical symptom of killing cancer cells. Here we find that USP7 expresses higher in ovarian cancer, USP7 absence delays ovarian cancer proliferation, and CDDO-Me could directly bind to USP7 and inhibit USP7 activity. Therefore USP7 is a novel target of CDDO-Me. Heat shock protein 90 is a highly conserved protein chaperone in eukaryote, through assiting folding, activating, maturation and assembling target protein to maintain cell inner environment. More and more evidence suggests that Hsp90 is a suitable target of treating cancer cell including ovarian cancer, in our research we find that CDDO-Me could directly bind to Hsp90 and inhibit Hsp90 activity, also CDDO-Me could induce Hsp90 downstream proteins change. Hence, Hsp90 is a new target of CDDO-Me too. New targets of CDDO-Me could provide new insights of clinical use in curing cancer and give more evidence in clinic use.