Carcinogenesis, 2011, 32(11):1675-83.

ERβ-specific agonists and genistein inhibit proliferation and induce apoptosis in the large and small intestine

B.Schleipen, et al

Abt. molekulare und zelluläre Sportmedizin, Institut für Kreislaufforschung und Sportmedizin, Deutsche Sporthochschule Köln, Am Sportpark Müngersdorf 6, 50933 Cologne, Germany

Epidemiological data indicate that intake of estrogens and isoflavones may be beneficial for the prevention of colorectal cancer (CRC). Based on this data, the aim of the study was to investigate estrogen receptor (ER) subtype-specific effects on intestinal homeostasis. Ovariectomized (OVX) female Wistar rats were either treated with 17β-estradiol (4 μg/kg body wt/day) (E2), an ERα-specific agonist (ALPHA) (10 μg/kg body wt/day), an ERβ-specific agonist (BETA) (100 μg/kg body wt/day) or genistein (GEN) (10 mg/kg body wt/day) for three weeks. Vehicle-treated OVX and SHAM animals and those cotreated with BETA and the pure antiestrogen Fulvestrant (ICI 182780) (100 μg/kg body wt/day and 3 mg/kg body wt/day) served as controls. GEN and BETA treatment but not E2 and ALPHA administration reduced proliferation in ileal and colonic mucosa cells. The rate of apoptosis in the small intestine and colon was increased by treatment with BETA and GEN, but not by E2. BETA induced antiproliferative and proapoptotic activity also in SHAM animals. The effects were antagonized by the pure antiestrogen Fulvestrant. Polymerase chain reaction gene array analysis revealed that BETA resulted in the downregulation of the oncogene transformation-related protein 63 (p63). Our data indicate that activation of the ERβ by specific ERβ agonists and GEN induces antiproliferative and proapoptotic effects in the intestinal tract. This observation can be taken as an indication that intake of GEN and specific ERβ agonists may protect the ileal and colonic epithelium from tumor development via modulation of tissue homeostasis.

英国《致癌作用》，2011年8月

ERβ-特异性受体激动剂和染料木黄酮在大肠和小肠中抑制细胞增殖并诱导其凋亡

B 施莱彭等

德国科隆大学研究所心血管研究、运动医学和细胞运动医学系

流行病学资料显示，雌激素和异黄酮的摄入可能有利于预防大肠癌 (CRC)。基于这个数据，本研究的目的是探讨雌激素受体 (ER) 的亚型特异性对肠道内环境稳态的影响。用 17β-雌二醇 （4ug/kg wt/天） (E2)，ERα-特定受体激动剂 （ALPHA） （10ug/kg wt/天）、和ERβ-受体激动剂 (BETA) （100 ug/kg wt/天） 或金雀异黄素 （GEN） （10 ug/kg wt/天）处理切除卵巢 的(OVX)雌性大鼠，为期三周。将安慰剂-处理的OVA和SHAM动物和那些用β和纯抗雌激素氟维司共处理 (ICI 182780) （100 μg/kg wt/天和3 mg/kg wt/天） 作为对照组。GEN和 BETA 的治疗而不是 E2 和ALPHA给药会减少回肠、 结肠粘膜细胞的增殖。通过用BETA和GEN而不是E2治疗提高小肠和结肠细胞的凋亡率。在SHAM动物中BETA也诱导抗增殖和凋亡的活性。纯抗雌激素氟维司抗拒这些作用。聚合酶链反应基因阵列分析显示， BETA导致了癌基因转换相关蛋白 63 (p63) 的下调。我们的数据表明在肠道内，通过特异性ERβ受体激动剂使ERβ活化，并且GEN诱导了抗增殖和细胞凋亡。从这种观察结果可以说明GEN的摄入和特异性ERβ 受体激动剂通过调节组织稳态可能防止回肠及结肠上皮细胞肿瘤的发展。