Jumonji domain-containing 6 (JMJD6) is a candidate gene associated with
tumorigenesis, and JMJD6 overexpression predicts poor differentiation and unfavorable survival in some
cancers. However, there are no studies reporting the expression of JMJD6 in
ovarian cancer, and no JMJD6 inhibitors have been developed and applied to targeted
cancer therapy research. In the present study, we found that the high expression of JMJD6 in
ovarian cancer was correlated with poor prognosis in
ovarian cancer. A potential inhibitor (SKLB325) was designed based on the crystal structure of the jmjC domain of JMJD6. This molecule significantly suppressed proliferation and induced apoptosis in a dose-dependent manner in SKOV3 cell lines as detected by
CCK-8 cell proliferation assays and flow cytometry. A
Matrigel endothelial tube formation assay showed that SKLB325 inhibited capillary tube organization and migration in HUVECs in vitro. We also observed that JMJD6 colocalized with p53
protein in the nucleus, with
mRNA and
protein expression of p53 as well as its downstream effectors significantly increasing both in vitro and in intraperitoneal
tumor tissues treated with SKLB325. In addition, SKLB325 significantly reduced the intraperitoneal
tumor weight and markedly prolonged the survival of
tumor-bearing mice. Taken together, our findings suggest that JMJD6 may be a marker of poor prognosis in
ovarian cancer and that SKLB325 may be a potential candidate drug for the treatment of
ovarian cancer.