Correlation of melatonin and estrogen receptor expression in breast cancer
-
摘要:
目的 研究褪黑素对大鼠乳腺癌组织中雌激素受体表达的影响,分析褪黑素在乳腺癌发生发展中的作用。 方法 选用2月龄清洁级雌性SD大鼠90只,接种大鼠乳腺癌细胞,随机分为注射生理盐水对照组、7.5 mg/(kg·d)注射褪黑素组、15 mg/(kg·d)注射褪黑素组,10 d后乳腺癌大鼠荷瘤模型建立成功并取乳腺癌组织,采用免疫组化法检测乳腺癌中雌激素受体的表达情况。 结果 注射褪黑素组的大鼠乳腺癌组织雌激素受体表达指数低于注射生理盐水对照组,随着注射褪黑素剂量上升,雌激素受体表达指数进一步下降,差异具有统计学意义(P<0.05)。 结论 褪黑素能抑制乳腺癌组织中雌激素受体的表达,可能是褪黑素拮抗乳腺癌发生发展的途径之一。 Abstract: Objective To study the effect of melatonin on the expression of estrogen receptor in rats breast cancer, and to analyze the role of melatonin in the development of breast cancer. Methods Ninety female rats of clean grade SD in age 2 months were selected, and the breast cancer cells were inoculated in the rats. The rats were randomly divided to control group injected with saline, group injected with melatonin at a dose of 7.5 mg/(kg·d), group injected with melatonin at a dose of 15 mg/(kg·d). The breast cancer tumor bearing models of rats were established on the 10th day after inoculating, and the tissues of breast cancer were taken out. The expression of estrogen receptor in breast cancer was detected by immunohistochemistry method. Results The estrogen receptor expression index of rats breast cancer tissues in the group injected with melatonin was lower than that in the control group injected with saline, the estrogen receptor expression index further decreased with the increase of the dose of melatonin. Above differences were statistically significant. Conclusion Melatonin can inhibit the expression of estrogen receptor in breast cancer tissues, which may be one of the ways to prevent the development of breast cancer.-
Key words:
- melatonin /
- breast cancer /
- estrogen receptor
-
表 1 不同分组大鼠乳腺癌组织雌激素受体表达情况(
$\, \overline{{x}}{{±}}{{s}}$ ,n=30)组别 ER表达指数(%) t P 注射生理盐水组 28.61±12.52 7.5 mg/(kg·d)注射褪黑素组 22.49±9.26 2.1526 <0.05* 15 mg/(kg·d)注射褪黑素组 18.02±7.17 2.0905 <0.05** *P<0.05vs注射生理盐水组;**P<0.05vs7.5 mg/(kg·d)注射褪黑素组. -
[1] Savukaitytė A, Ugenskienė R, Jankauskaitė R, et al. Investigation of prognostic value of polymorphisms within estrogen metabolizing genes in Lithuanian breast cancer patients[J]. BMC Med Genet, 2015, 16(8): 2. [2] Zekas E, Prossnitz ER. Estrogen-mediated inactivation of FOXO3a by the G protein-coupled estrogen receptor GPER[J]. BMC Cancer, 2015, 15(4): 702-7. [3] Schernhammer ES, Hankinson SE. Urinary melatonin levels and breast cancer risk[J]. J Natl Cancer Inst, 2005, 97(14): 1084-7. doi: 10.1093/jnci/dji190 [4] Haus EL, Smolensky MH. Shift work and cancer risk: potential mechanistic roles of circadian disruption, light at night, and sleep deprivation[J]. Sleep Med Rev, 2013, 17(4): 273-84. doi: 10.1016/j.smrv.2012.08.003 [5] Letra-Vilela R, Sá nchez-Sá nchez AM, Rocha AM, et al. Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin[J]. Mol Cell Endocrinol, 2016, 434(11): 238-49. [6] Chowdhury I, Sengupta A, Maitra SK. Melatonin: fifty years of scientific journey from the discovery in bovine pineal gland to delineation of functions in human[J]. Indian J Biochem Biophys, 2008, 45(5): 289-304. [7] Codenotti S, Battistelli M, Burattini S, et al. Melatonin decreases cell proliferation, impairs myogenic differentiation and triggers apoptotic cell death in rhabdomyosarcoma cell lines[J]. Oncol Rep, 2015, 34(1): 279-87. [8] Reiter RJ, Rosales-Corral SA, Manchester LC, et al. Melatonin in the biliary tract and liver: health implications[J]. Curr Pharm Des, 2014, 20(30): 4788-801. doi: 10.2174/1381612819666131119105826 [9] Wei JY, Li WM, Zhou LL, et al. Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation[J]. J Pineal Res, 2015, 58(4): 429-38. doi: 10.1111/jpi.2015.58.issue-4 [10] Sigurdardottir LG, Markt SC, Rider JR, et al. Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men[J]. Eur Urol, 2015, 67(2): 191-4. doi: 10.1016/j.eururo.2014.07.008 [11] Stevens RG. Light-at-night, circadian disruption and breast cancer: assessment of existing evidence[J]. Int J Epidemiol, 2009, 38(4): 963-70. doi: 10.1093/ije/dyp178 [12] González A, Alvarez-Garcí a V, Martí nez-Campa C, et al. In vivo inhibition of the estrogen sulfatase enzyme and growth of DMBA-induced mammary tumors by melatonin[J]. Curr Cancer Drug Targets, 2010, 10(3): 279-86. doi: 10.2174/156800910791190201 [13] Carascossa S, Dudek P, Cenni B, et al. CARM1 mediates the ligand-independent and tamoxifen-resistant activation of the estrogen receptor alpha by cAMP[J]. Genes Dev, 2010, 24(7): 708-19. doi: 10.1101/gad.568410 [14] Renoir JM. Estradiol receptors in breast cancer cells: associated co-factors as targets for new therapeutic approaches[J]. Steroids, 2012, 77(12): 1249-61. doi: 10.1016/j.steroids.2012.07.019 [15] Chuffa LG, Seiva FR, Fá varo WJ, et al. Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation[J]. Reprod Biol Endocrinol, 2011, 9(12): 108-14. [16] Maurice P, Daulat AM, Turecek R, et al. Molecular organization and dynamics of the melatonin MT receptor/RGS20/G(i) protein complex reveal asymmetry of receptor dimers for RGS and G(i) coupling[J]. EMBO J, 2010, 29(21): 3646-59. doi: 10.1038/emboj.2010.236 [17] Sanchez-Barcelo EJ, Mediavilla MD, Alonso-Gonzalez C, et al. Breast cancer therapy based on melatonin[J]. Recent Pat Endocr Metab Immune Drug Discov, 2012, 6(2): 108-16. doi: 10.2174/187221412800604581 [18] Cos S, González A, Martínez-Campa C, et al. Estrogen-signaling pathway: a Link between breast cancer and melatonin oncostatic actions[J]. Cancer Detect Prev, 2006, 30(2): 118-28. doi: 10.1016/j.cdp.2006.03.002 [19] Hill SM, Cheng C, Yuan L, et al. Age-related decline in melatonin and its MT1 receptor are associated with decreased sensitivity to melatonin and enhanced mammary tumor growth[J]. Curr Aging Sci, 2013, 6(1): 125-33. doi: 10.2174/1874609811306010016 [20] Srinivasan V, Spence DW, Pandi-Perumal SR, et al. Melatonin, environmental light, and breast cancer[J]. Breast Cancer Res Treat, 2008, 108(3): 339-50. doi: 10.1007/s10549-007-9617-5 [21] Treeck O, Haldar C, Ortmann O. Antiestrogens modulate MT1 melatonin receptor expression in breast and ovarian cancer cell lines[J]. Oncol Rep, 2006, 15(1): 231-5.