雌激素抑制大鼠肝癌肺转移机制研究

摘要

目的探讨雌激素对大鼠肝癌肺转移形成的影响及其可能的机制。方法将雌性大鼠随机分为切除卵巢组、对照组、假手术组和去卵巢后加雌激素组，建立大鼠肝癌模型。诱癌20周后观察肿瘤发生、肺转移的情况；免疫组织化学法检测4组成瘤大鼠肝癌组织中雌激素受体α（ERα）、磷酸化雌激素受体α（P-ERα）、肝细胞生长因子（HGF）和白介素6（IL-6）的表达；半定量逆转录聚合酶链反应法检测 ERα、HGF 及 IL-6的 mRNA 水平。结果切除卵巢组大鼠肝癌肺转移发生率明显高于其他3组（P ＜0.05）；大鼠肝癌肺转移发生率越高，肝癌组织中 HGF、IL-6的蛋白及分子水平表达越高（P ＜0.05），而 ERα的蛋白及分子水平表达越低（P ＜0.05）。结论雌激素可能通过下调 HGF 和 IL-6的表达来抑制肝癌肺转移的发生。%Objective To determine whether and how estrogen reduced lung metastasis of HCC in a rat model. Methods We con-ducted a rat HCC model in female rats induced by diethylnitrosamine(DEN)and N-nitrosomorpholine(NMOR),and rats were distributed into four groups:ovariectomy,sham operation,ovariectomy followed by 30 μg/(kg·d)body weight/ day 17α-Ethynylestradiol(EE2)sup-plementation,sexually intact controls. Results Here we showed that,60% lung metastasis was observed in the rats of ovariectomy group, whereas obviously lower lung metastasis was found in the rats of other three groups. Furthermore,the higher expression of interleukin-6(IL-6), hepatocyte growth factor(HGF)and the lower expression of estrogen receptor α(ERα),the higher lung metastasis of HCC we founded. Con-clusion Estrogen may inhibit hepatic tumor lung metastasis by suppression of HGF and IL-6 production.