Estrogen-related receptor α (ERRα) is considered to be a potential molecular target against several cancer types. We previously demonstrated that ERRα knockdown regulated tumor progression in uterine endometrial cancer. The purpose of this study was to elucidate the effects of XCT790, a selective inverse agonist of ERRα, on endometrial cancer.
HEC-1A and KLE cells, endometrial cancer cells with high expression of ERRα, and HEC-1A-derived xenograft mouse model were treated with XCT790. Cell proliferation was evaluated with WST-8 and colony formation assays. The cell cycle was examined with flow cytometry, fluorescent immunocytochemistry. The apoptotic effect was determined with TUNEL assay and caspase-3/7 assay. Proteins and mRNA levels were detected by western blotting and real-time PCR.
XCT790 significantly inhibited ERRα-induced transcriptional activity in a dose-dependent manner (P < 0.01) without reduction of mRNA level of ERRα. XCT790 suppressed colony formation and cell proliferation in a concentration- and time-dependent manner (P < 0.01), without cytotoxicity. Flow cytometry, fluorescence immunocytochemistry, and western blotting indicated that XCT790 induced apoptosis (P < 0.01), and caused cell cycle arrest at the mitotic phase. Western blotting revealed that XCT790 inhibited Akt/mTOR signaling pathway without the alteration of the expression level of PI3K. Additionally, XCT790 significantly suppressed tumor progression in the xenograft mouse model (P < 0.05). XCT790 induced apoptosis and decreased Ki-67 positive cells in tissue sections (P < 0.01).
The findings of the present study suggested that XCT790 could be a novel therapeutic agent in uterine endometrial cancer.
Clinical trial identification
Legal entity responsible for the study
Has not received any funding.
All authors have declared no conflicts of interest.