长期低氧条件下LOX促进胃癌转移的机制  

The mechanism of LOX promoting gastric cancer metastasis under longterm hypoxic conditions

作　　者：梁金娥 包博文 张晓洁 刘云鹏[1] 车晓芳[1] LIANG Jin′e;BAO Bowen;ZHANG Xiaojie;LIU Yunpeng;CHE Xiaofang(Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province,Department of Medical Oncologys of the First Hospital of China Medical University,Liaoning Province,Shenyang 110001,China)

机构地区：[1]中国医科大学附属第一医院肿瘤内科辽宁省肿瘤药物与生物治疗重点实验室,辽宁沈阳110001

出　　处：《中国医药导报》2019年第4期4-8,共5页China Medical Herald

基　　金：国家重点研发计划重大慢性非传染性疾病防控研究重点专项(2017YFC1308900);辽宁省自然科学基金项目(2015020457);留学人员科技活动项目择优资助(项目启动类)(辽人社函[2015]125号);辽宁省中央引导地方科技发展专项资金项目(2016007010);辽宁省沈阳市重点科技研发计划项目(17-230-9-01)

摘　　要：目的探讨赖氨酰氧化酶(LOX)促进低氧耐性胃癌(HRGC)细胞转移的机制。方法胃癌细胞系MGC803和BGC823常规培养,HRGC细胞系MGC803/hypo和BGC823/hypo培养于2%O_2条件下。Transwell法检测各胃癌细胞迁移能力差异;PCR检测各胃癌细胞LOX mRNA水平;siRNA瞬时沉默LOX表达;Western blot法检测各胃癌细胞LOX、AKT等表达变化及AKT通路活化情况。结果与亲本胃癌细胞比较,HRGC细胞的迁移能力显著增强(P <0.05),且LOX mRNA和蛋白表达水平明显增加(P <0.05);瞬时沉默LOX后,HRGC细胞的迁移能力显著下降(P <0.05)。与亲本胃癌细胞比较,HRGC细胞中AKT磷酸化水平明显增加;瞬时沉默LOX明显降低了HRGC细胞中的AKT磷酸化水平(P <0.05)。结论长期低氧条件下LOX上调,并通过活化AKT通路促进胃癌细胞转移。Objective To investigate the mechanism of lysyl oxidase(LOX)on metastasis promotion in hypoxia-resistant gastric cancer(HRGC)cells.Methods The gastric cancer cell lines,MGC803 and BGC823 were routinely cultured.HRGC cell lines,MGC803/hypo and BGC823/hypo were cultured under 2%O2 conditions.The migration ability of gastric cancer cells was detected by Transwell assay.LOX mRNA level was detected by PCR;LOX siRNA was used for LOX transiently silencing;Western blot was used to detect the protein level of LOX,AKT and the activation of AKT pathways.Results Compared with the parental gastric cancer cells,the migration ability of HRGC cells was significantly enhanced(P<0.05),the expression level of mRNA and protein of LOX were significantly increased(P<0.05).After transient silencing of LOX,the migration ability was significantly decreased in HRGC cells(P<0.05).Compared with parental gastric cancer cells,AKT phosphorylation was significantly increased(P<0.05),whereas AKT phosphorylation was significantly decreased after transient silencing of LOX in HRGC cells(P<0.05).Conclusion Long-term hypoxic conditions increase LOX and promote gastric cancer cell metastasis by activating the AKT pathway.

关 键 词：胃癌 低氧 赖氨酰氧化酶 AKT 

分 类 号：R735.2[医药卫生—肿瘤]