摘要目的:观察Wnt诱导分泌蛋白-2(WISP-2)对胃癌细胞增殖、凋亡和迁移的影响并探讨其分子机制。方法:选取2015年6月到2018年6月收集的112例胃癌组织和对应的癌旁组织作为研究对象。采用免疫组织化学观察胃癌组织和癌旁组织中WISP-2蛋白的表达。采用携带WISP-2基因和空载体的慢病毒感染胃癌细胞株MKN-28，建立WISP-2过表达细胞株(WISP-2组)和对照细胞株(对照组)。采用细胞计数试剂盒(CCK-8)分析两组细胞的增殖能力；采用异种肿瘤移植模型分析两组细胞在体内的生长；采用流式细胞术分析两组细胞的凋亡水平；采用Transwell分析两组细胞的迁移能力。采用蛋白质印迹法(Western blot)分析两组细胞WISP-2蛋白、凋亡相关蛋白与迁移相关蛋白的表达。采用 t检验和方差分析。 结果:胃癌组织中WISP-2蛋白的表达水平(89.43±7.51)较癌旁组织中WISP-2蛋白表达水平(193.42±12.09)显著下调，差异有统计学意义( t＝6.019， P<0.05)。WISP-2组细胞增殖(1.21±0.14)明显低于对照组(1.79±0.21)，差异有统计学意义( t＝2.916， P<0.05)。WISP-2组细胞在裸鼠中的肿瘤体积[(1 029.32±101.58) mm 3]明显小于对照组[(1 930.60±198.44) mm 3]，差异有统计学意义( t＝3.001， P<0.05)。WISP-2组细胞凋亡水平(21.45±4.91)较对照组(3.41±0.56)显著增加，差异有统计学意义( t＝2.819， P<0.05)。WISP-2组细胞迁移数量[(231.23±19.32)个]明显低于对照组细胞迁移数量[(98.21±10.32)个]，差异有统计学意义( t＝4.013， P<0.05)。WISP-2组细胞半胱氨酰天冬氨酸特异性蛋白酶(Caspase)-3和B细胞淋巴瘤/白血病-2相关X蛋白(bax)蛋白表达水平(1.94±0.34、1.53±0.19)较对照组Caspase-3和bax表达水平(0.98±0.24、0.55±0.10)显著增加，差异有统计学意义( t＝2.193、3.018， P<0.05)。WISP-2组细胞黏着斑激酶(FAK)蛋白表达水平(0.58±0.10)较对照组细胞FAK蛋白表达水平(1.27±0.17)显著下降，差异有统计学意义( t＝2.990， P<0.05)。 结论:WISP-2蛋白在胃癌组织中低表达，参与胃癌细胞增殖、凋亡和迁移。

abstractsObjective:To investigate the effect of Wnt-induced signaling protein-2 (WISP-2) on the proliferation, apoptosis and migration of gastric cancer cells and its molecular mechanism.Methods:112 cases of gastric cancer tissues and corresponding adjacent tissues collected from June 2015 to June 2018 were selected as the study subjects. The expression of WISP-2 protein in gastric cancer and adjacent tissues was analyzed by immunohistochemistry. The gastric cancer cell line MKN-28 was infected by lentivirus carrying WISP-2 gene and empty vector. The overexpression cell line of WISP-2 (WISP-2 group) and the control cell line (control group) were established. The proliferation ability of the two groups was analyzed by cell counting kit-8 (CCK-8). The tumor growth of WISP-2 group and control group in vivo was analyzed by xenogeneic tumor transplantation model. The apoptosis level in WISP-2 group and control group was analyzed by flow cytometry. The migration ability in WISP-2 group and control group was analyzed by Transwell assay. The expression of WISP-2 protein, apoptosis associated proteins and migration associated protein in the two groups was analyzed by Western blotting. Results:Compared with the paracancerous tissues (193.42±12.09), the expression level of WISP-2 protein in the gastric cancer tissues (89.43±7.51) was significantly down-regulated ( t=6.019, P<0.05). The cell proliferation of WISP-2 group (1.21±0.14) was significantly lower than that in the control group (1.79±0.21) ( t=2.916, P<0.05). The tumor volume in WISP-2 group [(1 029.32±101.58) mm 3] was significantly smaller than that in control group [(1 930.60±198.44) mm 3,t=3.001, P<0.05]. As compared with the control group (3.41±0.56), the apoptosis level of WISP-2 group (21.45±4.91) significantly increased ( t=2.819, P<0.05). The number of migrating cells in WISP-2 group [(231.23±19.32) cells] was significantly reduced as compared with that in the control group [(98.21±10.32) cells, t=4.013, P<0.05]. As compared with the control group (0.98±0.24, 0.55±0.10), the expression levels of Caspase-3 and bax in the WISP-2 group (1.94±0.34, 1.53±0.19) significantly increased ( t=2.193, 3.018, P<0.05). As compared with the control group (1.27±0.17), the expression level of FAK in the WISP-2 group (0.58±0.10) was significantly reduced ( t=2.990, P<0.05). Conclusion:WISP-2 protein is down-regulated in gastric cancer, which is involved in the proliferation, apoptosis and migration of gastric cancer cells.