肝X受体α与蛋白酶体激活因子28γ在胃癌中的表达及其对胃癌细胞生长的影响

Expressions of liver X receptor and proteasome activator 28 in gastric cancer and their effects on growth of gastric cancer cells

目的:探讨肝X受体α(LXRα)与蛋白酶体激活因子28γ(PA28γ)在胃癌中的表达以及两者对胃癌细胞生长的影响。方法:用qRT-PCR和免疫组织化学方法检测LXRα与PA28γ的mRNA与蛋白在35例胃癌和癌旁组织中的表达,分析LXRα与PA28γ蛋白表达与患者临床病理因素的关系以及两者的相关性。分别用流式细胞术、qRT-PCR、Westernblot检测过表达LXRα对胃癌AGS细胞的细胞周期、裸鼠体内生长以及细胞中LXRα对PA28γ表达的变化。结果:与癌旁组织比较,胃癌组织中LXRα的mRNA与蛋白表达明显降低,而PA28γ的mRNA与蛋白表达明显升高(均P<0.05);两者蛋白的表达与胃癌患者主要临床病理因素均无明显关系(均P>0.05);LXRα与PA28γ蛋白表达在胃癌组织中呈明显负相关(r=-0.452,P=0.006)。过表达LXRα后,AGS细胞的LXRα的mRNA表达明显升高,而PA28γ的mRNA与蛋白表达明显降低;细胞周期进程受到明显阻滞;在裸鼠体内的生长明显抑制,且移植瘤组织中的LXRα的mRNA与蛋白表达明显上调、PA28γ的mRNA与蛋白表达明显下调(均P<0.05)。结论:LXRα在胃癌中表达下调,同时伴随PA28γ表达上调,两者之间的消长可能通过影响细胞周期进程而调节胃癌细胞的生长。

Objective： To investigate the expressions of liver X receptor a （LXRα） and proteasome activator 28T （PA28y） in gastric cancer and their effects on the growth of gastric cancer cells. Methods： The mRNA and protein expressions of LXRα and PA28y in 35 specimens of gastric cancer and paired adjacent tissue were determined by qRT-PCR and immunohistochemical staining. The relations of their protein expressions with the clinicopathologic factors of the patients, and their correlationship were analyzed. In gastric AGS cells after overexpression with LXRα, the changes in cell cycle, growth in nude mice and expressions of LXRα and that of PA28y were analyzed by flow cytometr）5 qRT-PCR and Western blot, respectively. Results： Both mRNA and protein expressions of LXRα were significantly decreased, and both mRNA and protein expressions of PA28y were significantly increased in gastric cancer tissue compared with adjacent tissue （all P〈0.05）; the expressions of either LXRα or PA28T showed no significant associations with the main clinicopathologic factors of the gastric cancer patients （all P〉0.05）; there was a significant negative correlation between LXRα and PA28T protein expressions in gastric cancer tissue （r=-0.452, P=0.006）. In gastric AGS cells after overexpression with LXRα, the LXRα mRNA expression was significantly increased, while the mRNA and protein expressions of PA28T were significantly reduced, the cell cycle process was significantly blocked, the growth in nude mice was significantly suppressed, with significantly up-regulated mRNA and protein expressions of LXRα and down-regulated mRNA and protein expressions of PA283r in the tissue of the transplanted tumor （all P〈0.05）. Conclusion： LXRα expression is down-regulated in gastric cancer with synchronous up-regulated PA28T expression, and their growth and decline may probably regulate the growth of gastric cancer cells through affecting the cell cycle process.