低分子肝素对人胃癌裸鼠原位移植模型肿瘤生长、转移及趋化因子受体4表达的影响

Effect of low molecular weight heparin on growth,metastasis,and CXCR4 expression of orthotopicly transplanted gastric tumor in nude mice

目的:探讨低分子肝素(low molecular weight heparin,LMWH)对人胃癌裸鼠原位移植模型中肿瘤生长、转移及趋化因子受体4(chemokine receptor 4,CXCR4)表达的影响。方法:应用原位移植方法建立人胃癌裸鼠原位移植模型,模型建立后7 d时将裸鼠随机分为对照组(0.9%氯化钠溶液)、化疗组(5-氟尿嘧啶)和LMWH组(低分子肝素钙),分别每周给药2次,共5周。第6周牺牲动物,观察裸鼠胃癌原位模型的肿瘤生长及转移情况。应用RT-PCR和免疫组织化学法检测胃癌组织中CXCR4 mRNA和蛋白的表达水平。结果:化疗组和LMWH组的肿瘤体积比对照组明显缩小,差异有统计学意义(P<0.05);LMWH组胃癌原位模型的肿瘤转移率(20%)低于对照组(70%),差异有统计学意义(P<0.05),而与化疗组(11%)之间无明显差异(P>0.05);LMWH组CXCR4 mRNA和蛋白的表达均较对照组和化疗组下降,差异有统计学意义(P<0.05)。结论:LMWH具有抑制人胃癌裸鼠原位移植模型中肿瘤生长和转移的作用,可能与肿瘤组织中CXCR4表达下降有关。

Objective：To study the effect of low molecular weight heparin（LMWH） on tumor growth,metastasis,and the expression of chemokine receptor 4（CXCR4） in orthotopicly transplanted gastric tumor model in nude mice.Methods：The model of human gastric cancer was established by orthotopic transplantation of histologically intact tumor tissue blocks in the gastric walls of nude mice.On d 7 after transplantation all mice were randomly divided into 3 groups： control group（treated with normal saline）,LMWH group（treated with low molecular weight heparin calcium）,and chemotherapy group（treated with 5-fluorouracil）.The drugs were given twice a week for 5 weeks.Forty two days after treatment,tumor metastatic rates and tumor volume were recorded,respectively.The expressions of CXCR4 protein and mRNA were detected by immunohistochemistry and reverse-transcriptase polymerase chain reaction（RT-PCR）.Results：In comparison with that in the control group,the tumor volumes were significantly reduced in the LMWH group and chemotherapy group.The difference was significant（P0.05）.The tumor metastasis rate was significantly lower in LMWH group than that in control group（20% vs 70%,P0.05）.There was no significant difference between LMWH group and chemotherapy group（20% vs 11%,P0.05）.The expressions of CXCR4 protein and mRNA in the LMWH group were significantly decreased compared with those in the control group and chemotherapy group（P0.05）.Conclusion：LMWH has inhibitory effects on tumor growth and metastasis.The mechanism may be related with down-regulation of the expression of CXCR4 in tumor tissues.