Title
Author
DOI
Article Type
Special Issue
Volume
Issue
Effect of letrozole combined with testosterone on the proliferation and apoptosis of endometrial carcinoma cells
1 Xuzhou Medical University, Lianyungang 222002, P. R. China
2Reproductive Center, Lianyungang Hospital Affiliated to Xuzhou Medical University, Lianyungang 222002, P. R. China
DOI: 10.31083/j.ejgo.2020.04.5208 Vol.41,Issue 4,August 2020 pp.604-608
Submitted: 24 February 2019 Accepted: 03 June 2019
Published: 15 August 2020
*Corresponding Author(s): Chengxi Yang E-mail: dryangchengxi@163.com
Objective: To investigate the effect of the androgen testosterone on Ishikawa endometrial cancer (EC) cells in the presence of the aromatase inhibitor letrozole. Methods: Cultured Ishikawa EC cells were divided into three treatment groups: testosterone plus letrozole, testosterone alone and letrozole alone. The respective groups were treated for 48 h with these agents at final concentrations of 0.5, 1, 1.5, 2 or 2.5 µmol/L. The effect of combined letrozole and testosterone treatment was determined by MTT assay and flow cytometry. The effects of combined treatment on cell proliferation and apoptosis were also measured, while the concentration of estrogen in the culture solution was measured after treatment at a concentration of 2.5 µmol/L. Results: Inhibition of proliferation in the testosterone plus letrozole group increased with the concentration of these agents, with maximal inhibition observed at 2.5 µmol/L. Similarly, the rate of apoptosis increased with increasing concentration in the combined testosterone plus letrozole group. The proliferation and apoptosis rates were different between the three different testosterone and letrozole groups, while the estrogen concentration of the testosterone plus letrozole group was significantly lower that of the testosterone group. Conclusion: The androgen testosterone has anti-proliferative and pro-apoptotic effects on EC cells.
Endometrial cancer; Androgen; Antitumor; Proliferation; Apoptosis
Di Wu,Jirui Zhang,Chengxi Yang. Effect of letrozole combined with testosterone on the proliferation and apoptosis of endometrial carcinoma cells. European Journal of Gynaecological Oncology. 2020. 41(4);604-608.
[1] Labrie F.: “All sex steroids are made intracellularly in peripheral tissues by the mechanisms of intracrinology after menopause”. J. Steriod. Biochem. Mol. Biol., 2015, 145, 133.
[2] Gini Fleming F.: “SecondLine Therapy for Endometrial Cancer: The Need for Better Options. J. Clin. Oncol., 2015, 33, 3535.
[3] Allen N.E., Key T.J., Dossus L., et al.: “Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC)[J]”. Endocr. Relat. Cancer, 2008, 15, 485.
[4] Gotlieb W.H., Beiner M.E., Shalmon B., Korach Y., Segal Y., Zmira N., et al. “Outcome of fertilitysparing treatment with progestins in young patients with endometrial cancer”. Obstetr. Gynecol., 2003, 102, 718.
[5] AudetWalsh E., Lépine J., Grégoire J., Plante M., Caron P., Tétu B., et al.: “Profiling of endogenous estrogens, their precursors, and metabolites in endometrial cancer patients: association with risk and relationship to clinical characteristics”. J. Clin. Endocrinol. Metabol., 2011, 96, 330.
[6] Emons G., Heyl W.: “Hormonal treatment of endometrial cancer”. J Cancer Res Clin Oncol., 2000, 126, 619.
[7] Davis S.R.: “Cardiovascular and cancer safety of testosterone in women”. Curr. Opin. Endocrinol. Diabetes Obes., 2011, 18, 198.
[8] Dossus L., Lukanova A., Rinaldi S., Allen N., Cust A.E., Becker S., et al.: “Hormonal, Metabolic, and Inflammatory Profiles and Endometrial Cancer Risk Within the EPIC Cohort—A Factor Anal ysis”. Am. J. Epidemiol., 2013, 177, 787.
[9] Piltonen T.T.: “Polycystic ovary syndrome: Endometrial markers”. Best Pract. Res. Clin. Obstet. Gynaecol., 2016, 37, 1.
[10] Davis S.R., WahlinJacobsen S.: “Testosterone in women—the clin ical significance”. Lancet Diabetes Endocrinol.,2015, 3, 980.
[11] Clendenen T.V., Hertzmark K., Koenig K.L., Lundin E., Rinaldi S., Johnson T., et al: “Premenopausal Circulating Androgens and Risk of Endometrial Cancer: results of a Prospective Study”. Horm. Can cer, 2016, 7, 178.
[12] Zhao P.L., Zhang Q.F., Yan L.Y., Huang S., Chen Y., Jie Q., et al.: “Functional investigation on aromatase in endometrial hyperplasia in polycystic ovary syndrome cases”. Asian. Pac. J. Cancer Prev., 2014, 15, 8975.
[13] Li L., Feng W.: “Changes and significance of serum testosterone levels in patients with endometrial cancer”. Shandong Med. J., 2015, 68.
[14] Lanzino M., Sisci D., Morelli C., Garofalo C., Sebastiano A.: “In hibitor of cyclin D1 expression by androgen receptor in breast cancer cellsidentification of a novel androgen response element”. Nucleic Acids Res., 2010,38, 5351.
[15] Saito S., Ito K., Suzuki T., Utsunomiya H., Akahira J.I., Sugihashi Y., et al.: “Orphan nuclear receptor DAX1 in human endometrium asnd its disorders”. Cancer Science, 2005, 96, 645.
Top