Wang Ran, Li Ruixin, Wen Qiaocheng, Peng Kun, Tan Xiangzhou, Chen Zhikang
Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016 Feb;41(2):127-33. doi: 10.11817/j.issn.1672-7347.2016.02.003.
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.
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).
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.
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.
检测肝X受体-β（LXR-β）在人胃癌组织中的表达，并探讨LXRs激动剂GW3965对胃癌细胞系SGC-7901增殖的影响。
采用免疫组织化学法检测114例患者胃癌组织及相应癌旁组织中LXR-β、激活转录因子4（ATF4）的表达。运用实时定量PCR和蛋白质印迹法测定经或未经GW3965处理的SGC-7901细胞中ATF4及LXRs下游靶基因之一ATP结合盒转运体1（ABCA1）的mRNA和蛋白水平。采用细胞计数试剂盒-8（CCK-8）法检测细胞增殖情况。通过短发夹RNA（shRNA）沉默ATF4的表达。
胃癌组织中LXR-β和ATF-4的表达明显低于相应癌旁组织（均P<0.05）。与对照细胞相比，GW3965处理可抑制SGC-7901细胞增殖，并上调ATF4和ABCA1的表达（均P<0.05）。敲低ATF4可逆转GW3965对SGC-7901细胞的抗增殖作用。
人胃癌组织中LXR-β表达降低，GW3965激活LXRs可通过ATF4抑制SGC-7901细胞增殖。
