褪黑素联合MPA抑制子宫内膜异常增生的作用及机制研究

摘要 目的：探索褪黑素联合MPA（醋酸甲羟孕酮）对子宫内膜异常增生细胞增殖活性的抑制作用及其机制。方法：取分化良好的子宫内膜增生细胞株Ishikawa和内膜癌细胞株ECC1于适宜条件培养，加入褪黑素、MPA单独或者联合处理48 h后，检测子宫内膜细胞株的增殖活性。收集褪黑素、MPA单独或者联合处理48 h后的子宫内膜增生细胞株Ishikawa细胞，提取细胞内的蛋白，检测人20α-羟基类固醇脱氢酶（AKR1C1）的表达情况。结果：褪黑素和MPA联合使用后对子宫内膜异常增生细胞的抑制作用明显高于褪黑素或MPA单独使用。褪黑素和MPA可抑制AKR1C1的表达，二者联合使用对AKR1C1的抑制高于两者单独使用。结论：褪黑素可提高子宫内膜异常增生细胞对MPA的敏感性，降低MPA的使用剂量，同时抑制AKR1C1的表达，使孕酮的代谢速率降低。褪黑素与MPA联合使用给子宫内膜增生和内膜癌的治疗策略带来新的思路。

Inhibitory Effect and Mechanism of Melatonin Combined with MPA on Endometrial Hyperplasia

ABSTRACT Objective: To explore the inhibitory effect of melatonin combined with MPA on the proliferation of endometrial hyperplasia cells and its mechanism. Methods: The well differentiated endometrial hyperplasia cell line Ishikawa and endometrial cancer cell line ECC1 were cultured under appropriate conditions. After treatment with melatonin and MPA alone or in combination for 48 hours, the proliferative activity of endometrial cell lines was detected. The Ishikawa cells treated with melatonin and MPA alone or in combination for 48 h were collected, the protein was extracted, and the expression of AKR1C1 was detected. Ishikawa cell line overexpressing AKR1C1 was used to detect the cell proliferation activity after melatonin and MPA were treated alone or in combination for 48 hours. Results: The inhibitory effect of melatonin combined with MPA on endometrial cancer cells and endometrial dysplastic cells was significantly higher than that of melatonin or MPA alone. Melatonin and MPA can inhibit the expression of AKR1C1, and the inhibition of AKR1C1 in combination is higher than that in combination. Conclusion: Melatonin can improve the sensitivity of endometrial cancer to MPA, reduce the dosage of MPA, inhibit the expression of AKR1C1 and reduce the metabolic rate of progesterone. The combination of melatonin and MPA brings new ideas to the treatment strategy of endometrial hyperplasia.