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.
Highlights
Endometrial cancer is one of the most common gynecological malignancies, and its incidence has markedly increased around the world, especially in developed countries
The most strong inhibitory 2.acRteivsiutyltswas observed in the cell line RL95-2 with IC50 values of 19.88 μmol/L (95% confidence interval (CI): 12.01–32.91 μmol/L) at 48 h, we observed the IC50 values of 21.62 μmol/L haitb7it2edh Caneldl V5i2a.b8i0liμtyminola/LD(o9s5e%-DCepIe:n3d5e.8n5t –M77a.n7n7eμr mol/L) at 24 h (Table 1)
We investigated the effect of Nomegestrol acetate (NOMAC) on the mRNA expression levels of Wnt7a, β-catenin, suppressor of fused homolog gene (SUFU), PTCH2, and Gli2 to identify the pathway that mediated the effects of NOMAC on cell proliferation
Summary
Endometrial cancer is one of the most common gynecological malignancies, and its incidence has markedly increased around the world, especially in developed countries. Endometrioid adenocarcinoma accounts for over 80% of all endometrial cancers, and approximately 5–14% of affected women are younger than 40 years [1,2]. When arising in women of childbearing age, endometrial cancer usually presents with favorable prognostic features, including an endometrioid hystotype, a well-differentiated lesion, or/and an absent or minimal myometrial invasion, which belongs to type I endometrial cancer (estrogen/progesterone receptor (ER/PR) positive) [3,4]. The standard treatment for type I endometrial cancer is surgery and adjuvant therapy (e.g., progestin, radiotherapy, and chemotherapy) [5]. More efficacious and safer medical therapies are required to improve the management of type I endometrial cancer, especially for patients who are suffering endometrioid adenocarcinoma and wish to preserve fertility
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