Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice.
Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice.
复制标题
肝X受体激活抑制3-甲基胆蒽和丁基羟基甲苯诱导的BALB/c小鼠肺癌的发生
DOI：
10.1038/srep27295
复制
发表时间：
2016-06-02
影响因子：
4.6
通讯作者：
Duan Y
中科院分区：
文献类型：
--
作者：
Wang Q;Sun L;Yang X;Ma X;Li Q;Chen Y;Liu Y;Zhang D;Li X;Xiang R;Wei Y;Han J;Duan Y
我们之前报道过LXR配体T0901317通过激活IFN-γ的产生来抑制接种C57BL/6小鼠Lewis肺癌的生长。然而，T0901317对致癌物诱导的肺癌的作用尚不清楚。在本研究中，我们对TCGA数据库中提取的人类肺癌样本数据进行了初步的统计分析，确定肺癌患者的生存率/时间和肺腺癌分级分别与肺IFN-γ水平呈正相关和负相关。然后，我们测定了T0901317对3-甲基胆蒽（MCA）、丁基羟基甲苯（BHT）或氨基甲酸乙酯诱导的小鼠肺癌的抑制作用。我们发现T0901317通过抑制肺腺癌来降低MCA/ bht注射BALB/c小鼠的发病率和死亡率。T0901317对C57BL/6小鼠也有保护作用，但对IFN-γ缺乏（IFN-γ−/−，C57BL/6背景）小鼠，对MCA/ bht诱导的肺增生/炎症没有保护作用。此外，我们还确定了T0901317抑制聚氨酯诱导的BABL/c小鼠肺肿瘤。此外，我们确定T0901317可以阻止4T1乳腺癌细胞在BALB/c小鼠中的转移。给药T0901317可显著提高BABL/c和C57BL/6小鼠血清IFN-γ水平和肺IFN-γ表达。综上所述，我们的研究表明，LXR抑制MCA/ bht诱导的BABL/c小鼠肺癌，其抑制作用与诱导IFN-γ产生有关。
We previously reported that LXR ligand, T0901317, inhibited the growth of inoculated Lewis lung carcinoma in C57BL/6 mice by activating IFN-γ production. However, the effects of T0901317 on carcinogen-induced pulmonary carcinomas remain unknown. In this study, we initially conducted a statistical analysis on the data of human lung cancer samples extracted from the TCGA database, and determined that survival rate/time of lung cancer patients and grade of lung adenocarcinoma were positively and negatively related to lung IFN-γ levels, respectively. We then determined the inhibitory effects of T0901317 on mouse pulmonary carcinomas induced by 3-methylcholanthrene (MCA) and butylated hydroxytoluene (BHT) or urethane. We found that T0901317 reduced morbidity and mortality in MCA/BHT-injected BALB/c mice by inhibiting lung adenocarcinoma. T0901317 also protected C57BL/6 mice, but not IFN-γ deficient (IFN-γ−/−, C57BL/6 background) mice, against MCA/BHT-induced lung hyperplasia/inflammation. In addition, we determined that T0901317 inhibited urethane-induced lung tumors in BABL/c mice. Furthermore, we determined that T0901317 prevented metastasis of 4T1 breast cancer cells in BALB/c mice. Administration of T0901317 substantially increased serum IFN-γ levels and lung IFN-γ expression in BABL/c and C57BL/6 mice. Taken together, our study demonstrates that LXR inhibits MCA/BHT-induced pulmonary carcinomas in BABL/c mice and the inhibition is associated with induction of IFN-γ production.