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Nomegestrol Acetate Suppresses Human Endometrial Cancer RL95-2 Cells Proliferation In Vitro and In Vivo Possibly Related to Upregulating Expression of SUFU and Wnt7a.
Int J Mol Sci. 2017 Jun 22; 18(7)IJ

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.

Authors+Show Affiliations

Lab of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China. ayma14@fudan.edu.cn.Lab of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China. xieshw@fudan.edu.cn.Lab of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China. zjy_sans@sippr.org.Lab of Reproductive Pharmacology, Key Lab of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai 200032, China. zhuyan@sippr.org.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28640224

Citation

Ma, A-Ying, et al. "Nomegestrol Acetate Suppresses Human Endometrial Cancer RL95-2 Cells Proliferation in Vitro and in Vivo Possibly Related to Upregulating Expression of SUFU and Wnt7a." International Journal of Molecular Sciences, vol. 18, no. 7, 2017.
Ma AY, Xie SW, Zhou JY, et al. Nomegestrol Acetate Suppresses Human Endometrial Cancer RL95-2 Cells Proliferation In Vitro and In Vivo Possibly Related to Upregulating Expression of SUFU and Wnt7a. Int J Mol Sci. 2017;18(7).
Ma, A. Y., Xie, S. W., Zhou, J. Y., & Zhu, Y. (2017). Nomegestrol Acetate Suppresses Human Endometrial Cancer RL95-2 Cells Proliferation In Vitro and In Vivo Possibly Related to Upregulating Expression of SUFU and Wnt7a. International Journal of Molecular Sciences, 18(7). https://doi.org/10.3390/ijms18071337
Ma AY, et al. Nomegestrol Acetate Suppresses Human Endometrial Cancer RL95-2 Cells Proliferation in Vitro and in Vivo Possibly Related to Upregulating Expression of SUFU and Wnt7a. Int J Mol Sci. 2017 Jun 22;18(7) PubMed PMID: 28640224.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nomegestrol Acetate Suppresses Human Endometrial Cancer RL95-2 Cells Proliferation In Vitro and In Vivo Possibly Related to Upregulating Expression of SUFU and Wnt7a. AU - Ma,A-Ying, AU - Xie,Shu-Wu, AU - Zhou,Jie-Yun, AU - Zhu,Yan, Y1 - 2017/06/22/ PY - 2017/03/22/received PY - 2017/06/01/revised PY - 2017/06/10/accepted PY - 2017/6/23/entrez PY - 2017/6/24/pubmed PY - 2018/3/23/medline KW - KLE cells KW - RL95-2 cells KW - SUFU KW - Wnt7a KW - endometrial cancer KW - nomegestrol acetate KW - proliferation JF - International journal of molecular sciences JO - Int J Mol Sci VL - 18 IS - 7 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/28640224/Nomegestrol_Acetate_Suppresses_Human_Endometrial_Cancer_RL95_2_Cells_Proliferation_In_Vitro_and_In_Vivo_Possibly_Related_to_Upregulating_Expression_of_SUFU_and_Wnt7a_ L2 - http://www.mdpi.com/resolver?pii=ijms18071337 DB - PRIME DP - Unbound Medicine ER -