Epithelial ovarian cancer, widely suggested as endocrine-related cancer, yields a low survival rate among patients. Despite intensive research for nearly a century, there have been no fundamental advances in treatment. The reductive 17β-HSD7 is a special enzyme possessing a remarkable dual activity in both the biosynthesis of the most potent estrogen estradiol and the inactivation of the most active androgen dihydrotestosterone. In the present study, we observed over-expression of 17β-HSD7 in EOC cells such as OVCAR-3 and SKOV-3, in agreement with integrative data analysis demonstrating overexpression of 17β-HSD7 in EOC tissues. After knocking down 17β-HSD7, SKOV-3 cell proliferation decreased by 29%, cell arrest in the G2/M phase increased by 25% with cyclin B1/Cdk1 inhibition. Inhibition of 17β-HSD7 in EOC cells triggered negative feedback of its expression, which further decreased the estradiol level to more than 60% under the experimental condition. Such inhibition increased the dihydrotestosterone level to many times higher and suppressed cell proliferation. Thus, 17β-HSD7 is demonstrated to be a promising target for the endeavor against the malignant ovarian cancer, a menace in human life. The targeting of such an enzyme thus provides exceptional scientific importance.
Keywords: 17β-HSD type 7; G2/M cell-cycle arrest; cyclin B1/Cdk1 complex; dihydrotestosterone; estradiol.
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