Protective role of 17β-estradiol against the development of Helicobacter pylori-induced gastric cancer in INS-GAS mice
Protective role of 17β-estradiol against the development of Helicobacter pylori-induced gastric cancer in INS-GAS mice
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DOI：
10.1093/carcin/bgm150
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发表时间：
2007-12-01
期刊：
影响因子：
4.7
通讯作者：
Fox, James G.
中科院分区：
文献类型：
--
作者：
Ohtani, Masahiro;Garcia, Alexis;Fox, James G.
男性胃癌的发病率高于女性。流行病学研究表明，女性激素可降低胃癌风险。我们在高胃泌素血症 INS-GAS 小鼠中研究了卵巢依赖性雌性激素对幽门螺杆菌诱导的胃癌的影响。雄性和雌性性完整或卵巢切除 (OVX) 小鼠在 10 周龄时接种幽门螺杆菌 SS1 或仅用载体，并在感染后 16 或 28 周 (WPI) 评估组织。一部分 OVX 雌性从第 16 周开始补充 17 β-雌二醇 (E2)。通过组织病理学、Ki-67增殖指数、幽门螺杆菌定量培养和定量聚合酶链反应评估诱导型一氧化氮合酶（iNOS）和炎症细胞因子的信使RNA表达。在两个时间点，感染 OVX 的雌性比感染的未受感染的雌性出现更严重的胃炎 (P < 0.05)。对感染 OVX 的雌性进行 E2 治疗可减轻胃炎的严重程度。到 WPI 28 时，42% 的受感染雄性和 10% 受感染 OVX 雌性出现胃肠道上皮内瘤变 (GIN)，而受感染的完整雌性和 E2 治疗的 OVX 雌性没有出现 GIN。与未受感染的未受感染的雌性相比，受感染的 OVX 雌性表现出 iNOS 表达和上皮细胞增殖显着增加。同样，与未受感染的 OVX 雌性相比，受感染的 OVX 雌性在 28 WPI 中干扰素-γ、肿瘤坏死因子-α 和白细胞介素-1 β (IL-1 β) 的表达显着增加。感染 OVX 雌性的 E2 治疗显着降低了 IL-1 β 表达，增加了 IL-10 表达并减少了上皮细胞增殖。这些结果证明了 E2 对幽门螺杆菌诱导的小鼠模型胃癌的保护作用。
The incidence of gastric cancer is higher in men than women. Epidemiological studies suggest that female hormones reduce gastric cancer risk. We examined the effect of ovarian-dependent female hormones on Helicobacter pylori-induced gastric cancer in hypergastrinemic INS-GAS mice. Male and female sexually intact or ovariectomized (OVX) mice were inoculated with H.pylori SS1 or vehicle-only at 10 weeks of age, and tissues were evaluated at 16 or 28 weeks post-infection (WPI). A subset of OVX females were supplemented with 17 beta-estradiol (E2), beginning at 16 WPI. Stomachs were evaluated by histopathology, Ki-67 proliferation index, H.pylori quantitative culture and quantitative polymerase chain reaction for messenger RNA expression of inducible nitric oxide synthase (iNOS) and inflammatory cytokines. Infected OVX females developed significantly more severe gastritis (P < 0.05) than infected intact females at both time points. E2 treatment in infected OVX females attenuated the severity of gastritis. Gastrointestinal intraepithelial neoplasia (GIN) developed in 42% of infected males and 10% of infected OVX females by 28 WPI, whereas infected intact females and E2-treated OVX females did not develop GIN. Infected OVX females showed significantly increased iNOS expression and epithelial cell proliferation when compared with intact, infected females. Likewise, interferon-gamma, tumor necrosis factor-alpha and interleukin-1 beta (IL-1 beta) expression in infected OVX females were significantly increased at 28 WPI when compared with intact counterparts. E2 treatment in infected OVX females significantly decreased IL-1 beta expression, increased IL-10 expression and reduced epithelial cell proliferation. These results demonstrate a protective effect of E2 in H.pylori-induced gastric cancer in a mouse model.