Centre for Study of Liver Cancer, Affiliated Provincial Hospital, Anhui Medical University, No. 17, Lujiang Road, Hefei, 230001, China.
Inflammation. 2012 Feb;35(1):143-9. doi: 10.1007/s10753-011-9299-3.
Metastasis remains one of the major challenges before hepatocellular carcinoma (HCC) is finally conquered. Estrogen has recently emerged as a protective factor in the development and progression of HCC, but whether and how it reduces metastasis of HCC remain to be elucidated. We conducted an in vivo highly metastatic rat HCC model in female Sprague-Dawley rats induced by diethylnitrosamine and N-nitrosomorpholine to examine the effects of estrogen on HCC metastasis. Moreover, female rats were randomly distributed into four groups: ovariectomy (OVX), sham operation, ovariectomy followed by 30 μg/kg body weight/day 17α-ethynylestradiol supplementation, and sexually intact control groups. Here, we show that, 60% lung metastasis was observed in the rats of OVX group, whereas 17-25% lung metastasis was found in rats of the other three groups. Furthermore, physiological doses of estrogen, no matter endogenous or exogenous, can suppress metastasis of HCC through decreasing interleukin-6 (IL-6) and hepatocyte growth factor (HGF) expression in the tumor microenvironment. In conclusion, the present study demonstrated that estrogen has the potential to inhibit lung metastasis from rat HCCs in vivo. Its mechanism of action may involve modulation of inflammatory tumor microenvironment by suppression of HGF and IL-6 production.
转移仍然是肝癌（HCC）最终被攻克之前面临的主要挑战之一。最近，雌激素已成为 HCC 发生和进展的保护因素，但它是否以及如何减少 HCC 的转移仍有待阐明。我们在雌性 Sprague-Dawley 大鼠中建立了一种体内高转移性大鼠 HCC 模型，该模型由二乙基亚硝胺和 N-亚硝基吗啉诱导，以研究雌激素对 HCC 转移的影响。此外，雌性大鼠被随机分为四组：卵巢切除术（OVX）、假手术、卵巢切除术加 30μg/kg 体重/天 17α-乙炔雌二醇补充剂和性完整对照组。在这里，我们发现 OVX 组的大鼠有 60%发生肺转移，而其他三组的大鼠有 17-25%发生肺转移。此外，生理剂量的雌激素，无论是内源性还是外源性的，都可以通过降低肿瘤微环境中的白细胞介素 6（IL-6）和肝细胞生长因子（HGF）的表达来抑制 HCC 的转移。总之，本研究表明雌激素具有抑制大鼠 HCC 体内肺转移的潜力。其作用机制可能涉及通过抑制 HGF 和 IL-6 的产生来调节炎症性肿瘤微环境。
