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 cassette 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 P<0.05). Compared with the control cells, GW3965 treatment inhibited proliferation of SGC-7901 cells and up-regulated ATF4 and ABCA1 expressions (both P<0.05). 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.
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qRT-PCR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，shRNA)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)；shRNA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。.