基因芯片分析三肽化合物酪丝亮肽对人肝癌基因表达谱的影响  

Gene-chip analysis of the effect of tripeptide tyroserleutide on gene-expression in human hepatocarcinoma BEL-7402 tumors transplanted to nude mice

作　　者：孙亚军[1] 傅正[1] 朱志峰[1] 王莉[1] 贾静[1] 车绪春[1] 陆融[1,2] 林刚 姚智[1,3] 

机构地区：[1]天津医科大学基础医学院免疫学系,天津300070 [2]深圳市康哲药业有限公司,深圳518057 [3]教育部免疫微环境与疾病重点实验室,天津300070

出　　处：《天津医科大学学报》2013年第5期353-357,共5页Journal of Tianjin Medical University

基　　金：高校博士点基金资助项目(20101202110001);天津市应用基础与前沿计划重点项目(09JCZDJC19700);973国家重点基础研究发展计划(2009CB918903);广东省教育部产学研结合项目(2009B090300430)

摘　　要：目的:观察三肽化合物酪丝亮肽(YSL)的抗肿瘤作用,分析酪丝亮肽对肿瘤细胞基因表达情况的影响。方法:建立人肝癌BEL-7402裸鼠移植瘤模型,应用基因芯片技术分析酪丝亮肽对人肝癌BEL-7402裸鼠移植瘤肿瘤组织基因表达的影响,应用RT-PCR方法验证相关基因的表达情况。结果:给药剂量为160μg(/kg·d)时,酪丝亮肽能显著抑制裸鼠人肝癌BEL-7402移植瘤的生长,抑瘤率为41.34%,与生理盐水组比较均有统计学意义(P<0.05)。酪丝亮肽组与生理盐水组比较有33个基因变化倍数大于1倍以上,21个促进肿瘤增殖的基因表达下调,12个抑制肿瘤增殖的基因表达上调。结论:酪丝亮肽具有显著的抗肿瘤活性,可能是通过影响肿瘤细胞的PI3K信号转导通路,并籍此影响该通路的下游事件,损伤肿瘤细胞线粒体,诱导凋亡。Objective： To study effects of tyroserleutide （YSL） on tumor growth in nude mice and gene expression. Methods： The effects of YSL on human hepatocarcinoma BEL-7402 tumors transplanted in nude mice were observed. And gene expression in the tumor cells were detected by gene-chip analysis. The validation of gene expression data had been performed using semi-quantitative RT-PCR. Results： YSL significantly inhibited the growth of transplanted human hepatocarcinoma BEL-7402 tumors in BALB/c （nu/nu） nude mice compared with the control group （P〈0.05）, with an inhibition rate of 41.34% at 160 p,g/（kg-d）. A total of 202 genes were different between the YSL group and the control group, in which 33 genes changed in expression level by 1-fold or more including 21 down-regulated tumor genes and 12 up- regulated genes. Conclusion： YSL may exhibit a significant anti-tumor activity by inhibiting the PI3K signaling of tumor cells, thus damag- ing the functions of mitochondria which resuhs in apoptosis and necrosis of tumor cells.

关 键 词：肿瘤 酪丝亮肽 裸鼠 基因芯片 线粒体 PI3K 

分 类 号：R730.231[医药卫生—肿瘤] R735.7[医药卫生—临床医学]