Role of IL-6 in Progress of Estrogen Promoting Lung Adenocarcinoma in Mice and Its Mechanism
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摘要: 目的 探讨白介素6（interleukin 6, IL-6）在雌激素（estrogen, E2）促进小鼠肺腺癌进展中的作用及其可能的机制。方法 采用乌拉坦诱导雌性昆明小鼠建立肺腺癌模型，进行如下分组处理（每组9只）：空白对照组、E2组、雌激素抑制剂（E2 inhibitor, E2I）组、E2+E2I组、IL-6组、E2+IL-6组。小鼠饲养16周后处死检测小鼠体重变化、成瘤情况、肿瘤分级、肺脏器指数等指标，酶联免疫法（ELISA）检测对照组血清标本中E2/IL-6的含量，实时荧光定量PCR（Real-Time PCR, RT-PCR）检测对照组肿瘤标本中ERβ/IL-6的mRNA表达水平，采用免疫印迹法检测各组ERβ、Akt、MAPK,p-ERβ、p-Akt、p-MAPK表达水平。结果 肺部出现结节的昆明小鼠占小鼠总数的比例（即称为成瘤率）为87.04%（47/54），小鼠肺部结节做病理切片后证实为肺腺癌的小鼠数目占小鼠总数的比例（即成癌率）为70.37%（38/54），肺结节数、肿瘤指数、肺脏器指数等统计指标在E2组显著高于E2+E2I组、E2I组、E2+IL-6组、IL-6组及空白对照组（P均<0.05）；对照组小鼠血清中E2与IL-6呈高度相关性（P均<0.05），各组小鼠肺癌组织中Akt、MAPK、ERβ、p-AKt、p-MAPK、p-ERβ的表达水平及ERβ的mRNA表达水平与肿瘤统计指标表达的趋势相一致（P均<0.05）。结论 在E2促进小鼠肺腺癌进展过程中IL-6具有下调ERβ信号通路作用，提示IL-6可能抑制E2促进肺腺癌进展。Abstract: Objective To explore the role of IL-6 in the progress of Estrogen(E2) promoting lung adenocarcinoma in mice and its possible mechanism. Methods Urethane-induced lung adenocarcinoma models of female Kunming mice were established, and divided as follows(n=9 in each group): the control, E2, E2+estrogen inhibitors(E2I), E2I, IL-6 and E2+IL-6 group. 16 weeks later, we sacrificed mice and tested weight changes, tumorigenicity, the total number of nodules, tumor grade, and lung indices. At the same time, we detected the content of E2/IL-6 in serum specimens by enzyme-linked immunoassay (ELISA), ERβ/IL-6 mRNA levels by RT-PCR, and the protein expression of ERβ, Akt, MAPK, p-ER beta, p-Akt, p-MAPK by Western blot. Results The pulmonary nodules rate in Kunming mice were 87.04% (47/54); the lung adenocarcinoma rate were 70.37%(38/54); the total number of nodules, tumor grade, and lung indices in E2 group were significantly higher than those in E2+E2I and E2I group (P<0.05); and above detection index in E2 group was significantly higher than those in E2+IL-6, IL-6 group and blank control group (P<0.05); E2 and IL-6 in control group had highly correlations(P<0.05). The expression of Akt, MAPK, ER beta, p-Akt, p-MAPK, p-ER beta and ER beta mRNA were consistent with the cancer statistics index (P<0.05). Conclusion IL-6 downregulating ER beta signaling pathways is found in E2 promoting the progress of lung adenocarcinoma in mice for the first time, which indicates that IL-6 in lung cancer may inhibit E2 to promote lung adenocarcinoma progression.
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Key words:
- Interleukin 6(IL-6) /
- Estrogen(E2) /
- Lung adenocarcinoma
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