南方医科大学学报2018，Vol.38Issue(5)：511-519,9.
同种异体移植物炎症因子-1在结直肠癌细胞增殖、迁移及凋亡中的作用
Role of allograft inflammatory factor-1 in regulating the proliferation, migration and apoptosis of colorectal cancer cells
摘要
Abstract
Objective To investigate the role of allograft inflammatory factor-1 (AIF-1) in colorectal cancer (CRC) progression and explore the possible mechanism. Methods The expression levels of AIF-1 in 70 CRC tissues and paired adjacent tissues were detected using immunohistochemistry and Western blotting, and the correlation of AIF-1 expression with the clinicopathological features of the patients was analyzed.In the CRC cell line SW480,the functional role of AIF-1 in regulating tumor progression was investigated by transfecting the cells with an AIF-1-overexpressing plasmid (AIF-1) and a negative control plasmid (NC). EdU proliferation assay and flow cytometry were used to assess the cell proliferation and cell cycle changes;Transwell migration assay and Annexin V-APC/7-AAD apoptosis assay kit were used to analyze the cell migration and apoptosis.The changes in the biological behaviors of the cells were observed after application of SB203580 to block the p38 MAPK pathway. The expression levels of CDK4, cyclin D1, P21, P27, MMP2, MMP9, Bax, Bcl2, Bcl-xl, p38 and p-p38 were detected using Western blotting. Results AIF-1 was down-regulated in CRC tissues compared with the adjacent normal tissues, and its expression level was positively correlated with lymph node metastasis (P=0.008), TNM stage (P=0.003) and tumor size(P=0.023).Overexpression of AIF-1 in SW480 cells significantly reduced EdU-positive cells and caused obvious cell cycle arrest in G1 phase (P<0.05). AIF-1 overexpression resulted in significantly lowered protein expressions of CDK4 and cyclin D1, enhanced expressions of P21 and P27, attenuated cell migration ability (P<0.001), and decreased protein levels of MMP2 and MMP9.AIF-1 overexpression also induced obvious apoptosis of SW480 cells (P<0.01), significantly increased the protein levels of Bax and p-p38, and decreased the protein levels of Bcl-2 and Bcl-xl; SB203580 significantly attenuated the apoptosis-inducing effect of AIF-1 overexpression.Conclusion AIF-1 plays the role of a tumor suppressor in CRC by inhibiting cell proliferation,suppressing cell migration and inducing cell apoptosis.AIF-1 overexpression promotes the apoptosis of CRC cells by activating the p38 MAPK pathway.关键词
AIF-1/结肠直肠癌/增殖/迁移/凋亡Key words
allograft inflammatory factor-1/colorectal cancer/proliferation/migration/apoptosis引用本文复制引用
艾晓兰,姚芳,王晓睛,段东北,李科,胡子有,殷果,王梅,吴炳义..同种异体移植物炎症因子-1在结直肠癌细胞增殖、迁移及凋亡中的作用[J].南方医科大学学报,2018,38(5):511-519,9.基金项目
国家自然科学基金(81771340) （81771340）
南方医院院长基金(2015C003)Supported by National Natural Science Foundation of China(81771340). （2015C003）
