title: Estrogen suppresses metastasis in rat hepatocellular carcinoma through decreasing interleukin-6 and hepatocyte growth factor expression.
abstract: 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.
authors.affiliation: Centre for Study of Liver Cancer, Affiliated Provincial Hospital, Anhui Medical University, No. 17, Lujiang Road, Hefei, 230001, China.
authors.forename: Yong-Cang
authors.initials: YC
authors.lastname: Wang
authors.forename: Ge-Liang
authors.initials: GL
authors.lastname: Xu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Jia
authors.forename: Sheng-Jin
authors.initials: SJ
authors.lastname: Han
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Ren
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Liu
authors.forename: Chuan-Hai
authors.initials: CH
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D004052:Diethylnitrosamine; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000601:surgery; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D009602:Nitrosamines; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D004967:Estrogens; D015850:Interleukin-6; D009602:Nitrosamines; D004052:Diethylnitrosamine; C002741:N-nitrosomorpholine; D004997:Ethinyl Estradiol; D017228:Hepatocyte Growth Factor