肝X受体-β在胃癌组织中的表达及其激动剂GW 3965对胃癌细胞SGC-7901增殖的影响

Expression of LXR-β in human gastric cancer tissue and the effect of GW3965 on the proliferation of gastric cancer cell line SGC-7901

目的:探讨肝X受体-β(liver X receptor-β,LXR-β)在胃癌组织中的表达及其激动剂GW3965对胃癌细胞SGC-7901增殖的影响。方法:应用免疫组织化学法检测114例胃癌及其对应的114例癌旁组织中增殖相关基因LXR-β和转录活化因子4(activating transcription factor 4,ATF4)的表达;培养胃癌细胞SGC-7901,待GW3965激活LXR-β后,应用q RTPCR和Western印迹检测LXR-β下游基因三磷酸腺苷结合盒A1(ATP-binding cassette A1,ABCA1)和ATF4的表达,采用细胞增殖-毒性检测试剂盒检测细胞增殖情况;GW3965激活LXR-β后,利用ATF4短发夹RNA(short hairpin RNA,sh RNA)靶向沉默ATF4,检测细胞增殖情况。结果:LXR-β和ATF4在胃癌组织中的表达均显著低于其相应的癌旁组织(均P<0.05);GW3965激活LXR-β后,SGC7901细胞增殖明显受抑制,ABCA1和ATF4的表达明显上调(均P<0.05);sh RNA能显著抑制ATF4的表达,并阻断LXR-β激活后抑制细胞增殖的作用。结论:LXR-β在胃癌组织中呈低表达,活化的LXR-β可能通过ATF4抑制胃癌细胞的增殖。

Objective： To examine the expression of liver X receptor-β（LXR-β） in human gastric cancer tissue,and to explore the effect of GW3965, an agonist of LXRs, on proliferation of gastric cancer cell line SGC-7901.Methods： The immunohistochemical assay was used to detect the expression of LXR-β, activating transcription factor 4（ATF4） in gastric cancer tissues and the corresponding pericarcinoma tissues in 114 patients. Real-time quantitative PCR and Western blot were used to determine mRNA and protein levels of ATF4 and ATP-binding cassett e 1（ABCA1）, one of the downstream target genes of LXRs, in SGC-7901 cells with or without GW3965 treatment. Cell counting kit-8（CCK-8） assay was performed to detect cell proliferation. The expression of ATF4 was silenced by short hairpin RNA（shRNA）.Results： The expressions of LXR-β and ATF-4 were obviously down-regulated in the gastric cancer tissues than that in the corresponding pericarcinoma tissues（both P0.05）. Compared with the control cells, GW3965 treatment inhibited proliferation of SGC-7901 cells and up-regulated ATF4 and ABCA1 expressions（both P0.05）. Knockdown of ATF4 can reverse the antiproliferative effect of GW3965 on SGC-7901 cells.Conclusion： The expression of LXR-β is decreased in human gastric cancer tissues, and activation of LXRs by GW3965 could inhibit the proliferation of SGC-7901 cells via ATF4.