Nomegestrol Acetate Suppresses Human Endometrial Cancer RL95-2 Cells Proliferation In Vitro and In Vivo Possibly Related to Upregulating Expression of SUFU and Wnt7a

Abstract

Nomegestrol acetate (NOMAC) has been successfully used for the treatment of some gynecological disorders, and as a combined oral contraceptive with approval in many countries. In this study, we investigated the effects of NOMAC on human endometrial cancer cells in vitro and in vivo. The proliferation of human endometrial cancer cells (RL95-2 and KLE) were assessed using CCK-8 and EdU incorporation assays. Whole-genome cDNA microarray analysis was used to identify the effects of NOMAC on gene expression profiles in RL95-2 cells. RL95-2 xenograft nude mice were treated with NOMAC (50, 100, and 200 mg/kg) or medroxyprogesterone acetate (MPA; 100 and 200 mg/kg) for 28 consecutive days. The results showed that NOMAC significantly inhibited the growth of RL95-2 cells in a concentration-dependent manner, but not in KLE cells. Further investigation demonstrated that NOMAC produced a stronger inhibition of tumor growth (inhibition rates for 50, 100, and 200 mg/kg NOMAC were 24.74%, 47.04%, and 58.06%, respectively) than did MPA (inhibition rates for 100 and 200 mg/kg MPA were 41.06% and 27.01%, respectively) in the nude mice bearing the cell line of RL95-2. NOMAC altered the expression of several genes related to cancer cell proliferation, including SUFU and Wnt7a. The upregulation of SUFU and Wnt7a was confirmed using real-time quantitative polymerase chain reaction and Western blotting in RL95-2 cells and RL95-2 xenograft tumor tissues, but not in KLE cells. These data indicate that NOMAC can inhibit the proliferation of RL95-2 cell in vitro and suppress the growth of xenografts in the nude mice bearing the cell line of RL95-2 in vivo. This effect could be related to the upregulating expression of SUFU and Wnt7a.

Metformin Enhances Nomegestrol Acetate Suppressing Growth of Endometrial Cancer Cells and May Correlate to Downregulating mTOR Activity In Vitro and In Vivo

“…MPA was generally used against EC in clinical trials, but its directly suppressive effects on EC cells were seldom mentioned. In the present study, MPA did not demonstrate strong inhibition on the growth of the three types of cell lines, which is consistent with our previous findings [31]. As for LNG and CPA, both of them exhibited stronger inhibitory capability than NOMAC in type I cells but demonstrated weaker inhibition than NOMAC in type II cells.…”

“…Based on the findings above, the suppressive effects of NOMAC on type I and type II cells were further investigated, taking RL95-2 and HEC-1A cells as examples. It was previously found that NOMAC impeded the proliferation of RL95-2 cells through interfering EdU (5-ethynyl-20-deoxyuridine) -incorporation [31]. Here, we further observed that NOMAC induced cell arrest at G0/G1 phase, promoted apoptosis, and increased the percentage of dead cells in a manner of concentration dependence in both RL95-2 and HEC-1A cells.…”

“…The longer half-life and less adverse effects of NOMAC lead to it being successfully used in contraception and in the treatment of many hormone-dependent gynecological disorders, including menstrual disturbances, heavy menstrual bleeding, and premenstrual syndrome [28,29,30]. Preliminarily, we found that NOMAC inhibited the growth of RL95-2 EC cells and the inhibitory effect was stronger than that of MPA [31]. Whether or not NOMAC effectively suppresses the growth of other types of EC cells is yet to be probed.…”

Comparison of Proangiogenic Effects of Adipose-Derived Stem Cells and Foreskin Fibroblast Exosomes on Artificial Dermis Prefabricated Flaps

“…The cells were then divided into two groups: an ADSC-Exo group and an HFF-Exo group. HUVECs were cocultured with 100 μg/ml ADSC-Exo or HFF-Exo for 24 h, and the effects of the respective exosomes on cell proliferation were detected using a 5-ethynyl-2 deoxyuridine (EdU) assay kit (RiboBio, Guangzhou, China) [18], according to the manufacturer's instructions. The cells were finally observed under a fluorescence microscope (Zeiss HLA100, Shanghai, China).…”

Human Adipose-Derived Stem Cells Promote Seawater-Immersed Wound Healing by Activating Skin Stem Cells via the EGFR/MEK/ERK Pathway

“…An EdU kit (Ribo, Guangzhou, China) was used to detect the effect of hADSCs on the proliferation of SW-treated cells [17]. The HaCaT cells were seeded at 1 × 10 5 cells/well in 24-well plates and cultured normally until their confluency was 70-80%.…”