An unprecedented endocrine target for ovarian cancer: inhibiting 17β-HSD7 supresses cancer cell proliferation and arrests G2/M cycle

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 17 beta-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 17 beta-HSD7 in EOC cells such as OVCAR-3 and SKOV-3, in agreement with integrative data analysis demonstrating overexpression of 17 beta-HSD7 in EOC tissues. After knocking down 17 beta-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 17 beta-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, 17 beta-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.

Automated summary

The upregulation of 17 beta-HSD7 in epithelial ovarian cancer cells leads to increased proliferation, which can be significantly reduced by knocking down the enzyme. Inhibition of 17 beta-HSD7 also results in negative feedback, lowering estradiol levels and increasing dihydrotestosterone levels, ultimately suppressing cell proliferation. Therefore, targeting 17 beta-HSD7 shows promise as a therapeutic strategy against malignant ovarian cancer.