自噬相关蛋白在胃癌中表达的临床意义

Clinical Significance of Autophagy-related Protein Expressed in Gastric Cancer

探讨自噬相关蛋白mTOR、Beclin1、ULK、p62在胃癌中表达的临床意义及自噬在胃癌中的作用。应用免疫组化法检测正常细胞、癌旁细胞及癌细胞中mTOR、Beclin1、ULK、p62蛋白的表达情况,以胃癌细胞株为研究模型,采用自噬抑制剂雷帕霉素和氯喹处理细胞后使用MTT实验检测胃癌细胞的活力,使用Transwell实验检测胃癌细胞的侵袭迁移能力。结果显示,肿瘤细胞组与癌旁细胞组相比,mTOR蛋白表达含量显著降低(p<0.05),Beclin1、ULK、p62各蛋白表达含量显著升高(p<0.05);采用不同浓度自噬抑制剂雷帕霉素处理细胞后,0 nmol/L组、0.1 nmol/L组、1 nmol/L组、10 nmol/L组、100 nmol/L组之间细胞增值抑制率差异有统计学显著性(n=6,F=136.864,p<0.05);采用不同浓度自噬抑制剂氯喹处理细胞后,0μmol/L组、5μmol/L组、10μmol/L组、15μmol/L组、20μmol/L组之间细胞增值抑制率差异有统计学显著性(n=6,F=1086.891,P<0.05)。研究表明,自噬相关蛋白mTOR、Beclin1、ULK、p62均参与了胃癌的发生,mTOR低表达及Beclin1、ULK、p62高表达可能与促进胃癌发生有密切关系,并提示自噬活性的增强可能促进了胃癌的发生及发展。

This paper studied the clinical significance of autophagy-related proteins mTOR,Beclin1,ULK(serine-threonine kinases),and p62 expressed in gastric cancer and the role of autophagy in gastric cancer.In the study,the immunohistochemistry was used to test the expression of mTOR,Beclin 1,ULK and p62 proteins in normal cells,precancerous cells and cancer cells,and the MTT experiment and Transwell experiment were applied to respectively detect the vitality and the invasion and migration ability of the gastric cancer cells,after processing the gastric cancer cell lines,as the research model,with the autophagy inhibitors rapamycin and chloroquine.It turned out that,(a)compared with the precancerous cells,the level of mTOR protein expression in gastric cancer cells was significantly reduced(p<0.05),and the levels of Beclin 1,ULK,and p62 protein expressions were significantly increased(p<0.05).(b)after processing cells with different concentrations of autophagy inhibitor rapamycin,the differences of cell proliferation inhibition rate among 0 nmol/L,0.1 nmol/L,1 nmol/L,10 nmol/L,and 100 nmol/L groups were statistically prominent(n=6,F=136.864,p<0.05).(c)after processing cells with different concentrations of autophagy inhibitor chloroquine,the differences of cell proliferation inhibition rate among 0μmol/L,5μmol/L,10μmol/L,15μmol/L,and 20μmol/L groups were statistically prominent(n=6,F=1086.891,p<0.05).The results show that the autophagy-related proteins mTOR,Beclin 1,ULK,and p62 were all involved in the occurrence of gastric cancer,and the low expression of mTOR and high expression of Beclin 1,ULK,and p62 may be closely related to the promotion of gastric cancer,and that the increase of autophagy activity may promote the occurrence and progression of gastric cancer.