抑癌基因PDCD4的表达对南蛇藤提取物抑制人胃癌裸鼠移植瘤生长的影响

Effect of tumor suppressor gene PDCD4 expression level on inhibition of human gastric cancer xenograft growth in nude mice by Celastrus Orbiculatus extract

目的探讨抑癌基因程序性细胞死亡因子4(PDCD4)的表达变化在南蛇藤提取物(COE)抑制人胃癌裸鼠皮下移植瘤生长中的作用。方法将外源性重组真核质粒pcDNA3.1-PDCD4转染到人胃癌细胞SGC-7901内,经G418筛选并建立高表达PDCD4的稳定转染细胞。同时建立胃癌裸鼠皮下移植瘤模型,随机分为对照组、pcDNA3.1组、pcDNA3.1-PDCD4组、COE组、pcDNA3.1+COE组、pcDNA3.1-PDCD4+COE组。观察各组移植瘤生长状况、免疫组织化学法检测移植瘤组织内PDCD4、E-cadherin、N-cadherin、Vimentin蛋白表达情况。结果pcDNA3.1-PDCD4组、COE组、pcDNA3.1+COE组、pcDNA3.1-PDCD4+COE组与对照组相比,均可抑制肿瘤的生长(P<0.05),抑瘤率分别为59.29%、57.52%、58.41%、71.68%;均可上调PDCD4、Ecadherin蛋白的表达,下调N-cdherin、Vimentin蛋白的表达(P<0.05)。pcDNA3.1-PDCD4+COE组与其余3组相比,抑瘤率更高(P<0.05),PDCD4、E-cadherin、N-cdherin、Vimentin蛋白表达水平的变化更大(P<0.05)。结论抑癌基因PDCD4可能参与COE对胃癌裸鼠皮下移植瘤生长的抑制作用,其机制可能与影响上皮间质转化(EMT)过程有关。

Objective To investigate the effect of tumor suppressor gene programmedcelldeath 4(PDCD4)expression level on inhibition of human gastric cancer xenograft growth in nude mice by Celastrus Orbiculatus extract(COE).Methods The exogenous recombinant eukaryotic plasmid pcDNA3.1-PDCD4 was transfected into human gastric cancer cell line SGC-7901,after screened by G418,a stable transfected cell line with high expression of PDCD4 was established.The subcutaneously transplant tumor model of human gastric cancer in nude mice was established and randomly divided into the control group,pcDNA3.1 group,pcDNA3.1-PDCD4 group,COE group,pcDNA3.1+COE group,and pcDNA3.1-PDCD4+COE group.The growth status and tumorigenic incubation period of xenograft were monitored,and protein expression level of PDCD4、E-cadherin、N-cdherin and Vimentin in xenograft was detected by immunohistochemistry assay.Results Compared with the control group,the tumor inhibition rates of pcDNA3.1-PDCD4 group,COE group,pcDNA3.1+COE group,pcDNA3.1-PDCD4+COE group were 59.29%,57.52%,58.41%,71.68%,respectively.The protein expression level of PDCD4,E-cadherin was significantly up-regulated,while the protein expression level of N-cadherin,Vimentin significantly decreased.In pcDNA3.1-PDCD4+COE group,the tumor inhibition rate and the changes of PDCD4、E-cadherin、N-cdherin and Vimentin protein expression levels were significant higher than other groups(P<0.01).Conclusion The tumor suppressor gene PDCD4 may be involved in the inhibitory effect of COE on the growth of human gastric carcinoma xenograft tumor in nude mice,and its mechanism may be related to the influence of EMT process.