摘要目的:观察含有WW结构域的氧化还原酶(WWOX)对胃癌细胞增殖、迁移和侵袭的影响。方法:收集南阳市中心医院2015年8月到2019年8月经手术切除的189例胃癌组织和癌旁组织作为研究对象，采用免疫组织化学分析WWOX蛋白的表达水平。采用过表达WWOX和对照质粒的慢病毒感染胃癌细胞SGC-7901，建立稳定细胞株，分为WWOX组和对照组。采用细胞计数试剂盒(CCK-8)和5-乙炔基-2’脱氧尿嘧啶核苷(EdU)分析两组细胞的增殖情况；采用Transwell分析两组细胞的迁移和侵袭水平。采用蛋白质印迹法(Western blot)分析两组细胞的细胞核增殖抗原(Ki-67)、黏着斑激酶(FAK)、基质金属蛋白酶(MMP)-2和迁移侵袭抑制蛋白(MIIP)蛋白的表达水平。计量数据比较采用 t检验。 结果:胃癌组织中WWOX蛋白水平(89.33±7.12)较癌旁组织WWOX蛋白水平(190.32±13.09)明显下降，差异有统计学意义( t＝3.142， P<0.05)。WWOX组细胞增殖(0.91±0.39)较对照组细胞增殖(1.79±0.51)显著下降，差异均有统计学意义( t＝2.901， P<0.05)。WWOX组细胞EdU阳性率[(39.78±5.44)%]较对照组细胞EdU阳性率[(87.51±7.01)%]显著下降，差异均有统计学意义( t＝3.182， P<0.05)。WWOX组迁移和侵袭细胞数量[(55.19±4.11)、(34.11±3.71)个]较对照组细胞迁移数量[(103.49±5.10)、(83.16±4.81)个]明显下降，差异有统计学意义( t＝2.710、2.372， P<0.05)。与对照组细胞Ki-67、FAK和MMP-2表达水平(1.21±0.15、0.83±0.11和1.28±0.20)比较，WWOX组细胞Ki-67、FAK、MMP-2和MIIP蛋白表达水平(0.69±0.12、0.31±0.09和0.71±0.15)明显下降，差异有统计学意义( t＝2.900、2.515， P<0.05； t＝2.879， P<0.05)。 结论:WWOX蛋白在胃癌组织中低表达，通过抑制细胞、迁移和侵袭起抑癌基因的作用。

abstractsObjective:To investigate the effect of the oxidoreductase gene containing the WW domain-containing oxidoreductase (WWOX) on proliferation, migration and invasion of gastric cancer cells and its molecular mechanism.Methods:189 cases of gastric cancer tissues and para-carcinoma tissues surgically removed in Nanyang Central Hospital from August 2015 to August 2019 were collected as the study objects, and the expression levels of WWOX protein were analyzed by immunohistochemistry. WWOX overexpression stable cell lines and control stable cell lines were established by lentivirus overexpressing WWOX and control plasmid, which were divided into WWOX group and control group. Cell proliferation was analyzed by cell counting kit-8 (CCK-8) and 5-Ethynyl-2’-deoxyuridine (EdU). The levels of cell migration and invasion in both group were analyzed by Transwell. The expression levels of proliferation cell nuclear antigen (Ki-67), focal adhesion kinase (FAK), matrix metalloproteinase (MMP)-2 and migration and invasion inhibitory protein (MIIP) proteins in the two groups were analyzed by Western blotting.Results:The level of WWOX protein in gastric cancer tissues (89.33±7.12) was significantly lower than that in para-carcinoma tissues (190.32±13.09, t=3.142, P<0.05). The proliferation of cells in WWOX group (0.91±0.39) was significantly lower than that in the control group (1.79±0.51, t=2.901, P<0.05). The EdU positive rate of cells in WWOX group [(39.78±5.44)%] was significantly lower than that in the control group [(87.51±7.01)%, t=3.182, P<0.05]. The migration and invading cells in WWOX group [(55.19±4.11), (34.11±3.71) cells] significantly decreaseed than control group [(103.49±5.10), (83.16±4.81) cells, t=2.710, 2.372, P<0.05]. Compared with the expression levels of Ki-67, FAK and MMP-2 (1.21±0.15, 0.83±0.11 and 1.28±0.20) in the control group, the expression levels of Ki-67, FAK, MMP-2 and MIIP proteins in the WWOX group (0.69±0.12, 0.31±0.09 and 0.71±0.15) were significantly decreased ( t=2.900, 2.515, 2.879, P<0.05). Conclusion:WWOX protein is down-expressed in gastric cancer tissues and as an anticancer gene by inhibiting cell, migration, and invasion.