%0 Journal Article
%T Estrogen Inhibits Colon Polyp Formation by Reducing Angiogenesis in a Carcinogen-Induced Rat Model
%A Jia Yang
%A Li-juan Xiong
%A Fei Xu
%A Xiang Zhao
%A Bo Liu
%A Kai-Lin Cai
%A Guo-bin Wang
%J International Journal of Endocrinology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/453898
%X Objective. To study the effects of estrogen on colon polyp formation, proliferation, and angiogenesis on a rat model of colon cancer induced by dimethylhydrazine (DMH). Methods. Thirty-six female ovariectomized (OVX) rats were randomly divided into 3 groups: (I) control group (administrated with vehicles weekly), (II) DMH group (administrated with DMH weekly), and (III) DMH + E2 group (administrated with DMH and 17 -estradiol weekly). The incidence, volumes, and multiplicity of colon polyps in each group were evaluated. The microvessel density (MVD), the expressions of Proliferating Cell Nuclear Antigen (PCNA), and the expressions of HIF-1¦Á and VEGF in polyps were detected in each group. Results. Estrogen reduced the multiplicity, volumes, and the PCNA expressions of DMH-induced colon polyps. The MVD in DMH + E2 group was significantly lower than that in DMH group. Estrogen treatment decreased the HIF-1¦Á and VEGF expressions at both mRNA and protein level. Conclusion. Estrogen replacement was protective for ovariectomized rats from DMH-induced carcinogenesis, and one of the mechanisms for this was due to estrogen¡¯s inhibitive effects on blood vessel formation by downregulating VEGF and HIF-1¦Á expressions. 1. Introduction Plenty of epidemiologic evidence demonstrated that estrogen might influence the incidence of colon cancer in women [1¨C3]. Colon cancer risk increased after menopause and decreased after hormone replacement treatment (HRT) [4]. Many hypotheses had been proposed and studied. Estrogen receptors were found in colon epithelium and the estrogen receptor beta was the dominant subtype [5]. On cell models, many studies had found that estrogen could affect the growth of cells originated from colon mucosa [6, 7]. On an animal model of rats induced by DMH, we have found that ovariectomy could promote colon tumor formation [8]. Since the angiogenesis was vital for tumorigenesis and the estrogen was a well-known vasoactive hormone, it was worth investigating whether estrogen could influence angiogenesis in the course of colon carcinogenesis. There were several types of vasculation during carcinogenesis, including angiogenesis, vasculogenesi, and vasculogenic mimicry. In early stage of cancer, the main type of vessel formation was angiogenesis [9], triggered by proangiogenic factors [10]. Among the pro-angiogenic factors, VEGF was the essential factor in angiogenesis [11, 12]. In the present study, we studied the effects of estrogen on the microvessel density (MVD) and the expression of VEGF and its main upstream regulator HIF-1¦Á. 2. Material and
%U http://www.hindawi.com/journals/ije/2013/453898/