褪黑素对乳腺癌的抑制作用

摘要

Melatonin has a significant inhibitory effect on various cancers,especially on breast cancer.In estrogen receptor (ER)-positive human breast cancer,anti-cancer effects ofmelatonin on breast cancer cells and transplanted tumors mainly achieve by suppressing ER mRNA expression and ER transcriptional activity via the MT1 receptor.In addition,melatonin regulates the transactivation of other members of the nuclear receptor super-family,estrogen metabolizing enzymes,and the expression of related genes.Furthermore,melatonin also suppresses tumor aerobic metabolism,critical cell-signaling pathways relevant to cell proliferation,survival,metastasis,and drug resistance.Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell-type specific.Studies on animal and human models indicate that disruption of the circadian nocturnal melatonin signal promotes the growth,metabolism,and signaling of human breast cancer,resulting in invalid hormone therapy and chemotherapeutic resistance in breast tumors.%褪黑素对多种肿瘤尤其是乳腺癌有明显抑制作用.在雌激素受体(estrogen receptor,ER)阳性的乳腺癌中,褪黑素对乳腺癌细胞和移植瘤的抗癌作用主要是通过其受体MT1介导抑制ER mRNA的表达与ER的转录活性而实现;褪黑素还可调节核受体超家族中其他受体和雌激素代谢酶的转录激活及相关基因的表达,并能抑制肿瘤的有氧代谢和细胞增殖、生存、转移和耐药的关键通路.在乳腺癌细胞中表现出细胞特异性的细胞生长抑制作用和细胞毒作用.人类和动物模型的研究均表明褪黑素昼夜节律的紊乱促进了人类乳腺癌生长、代谢和信号转导,进而驱动了乳腺肿瘤内分泌治疗无效和化疗耐药.