三肽化合物酪丝缬肽对人肝癌裸鼠移植瘤基因表达谱的影响  

Effect of tripeptide compound tyroservaltide on gene expression profile in human hepatocarcinoma BEL-7402 transplanted tumor in nude mice

作　　者：王松[1] 陆融[1] 朱智彤[1] 赵茜[1] 卢奕[1] 贾静[1] 傅正[1] 周春雷[1] 赵岚[1] 李会强[1] 李鸿钊[1] 姚智[1] 

机构地区：[1]天津医科大学免疫学教研室,天津300070

出　　处：《肿瘤》2006年第8期699-704,共6页Tumor

基　　金：国家"863"高技术研究发展计划资助项目(编号2004AA2z3170;2005AA2Z3D40);国家"973"基础研究资助项目(编号:2003CCA04300);教育部重点项目(编号:03007)

摘　　要：目的：观察小分子三肽化合物酪丝缬肽(tyroservatide,YSV)的抗肿瘤作用,分析YSV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YSV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320μg·kg^(-1)·d^(-1)时,YSV能显著抑制裸鼠人肝癌BEL-7402移植瘤的生长,抑瘤率为52.37%,与生理盐水组比较均有统计学意义(P＜0.05)。YSV组与生理盐水组比较有781个基因存在统计学差异,其中52个基因与抑瘤效果密切相关,37个促进肿瘤增殖的基因表达下调,15个抑制肿瘤增殖的基因表达上调。RT-PCR检测证实YSV能够明显抑制肿瘤细胞癌基因Akt与上调抑癌基因PTEN的表达。结论：YSV具有显著的抗肿瘤活性,可以抑制肿瘤增殖相关基因的表达,增强抑制肿瘤生长相关基因的表达水平,以恢复它们之间的平衡关系,达到抗肿瘤细胞效应。Objective： To observe the anti-tumor effects of a bioactive tripeptide, tyroservaltide （YSV）, and analyze its influence on gene expression profile of tumor cells. Methods： Transplanted tumor model was established by implanting human hepatocarcinoma BEL-7402 cells into nude mice. Gene expression profile in the tumor cells was assayed by gene-chip analysis. Semiquantitative reverse transcription-polymerase chain reaction （RT-PCR） was used to verify the result of the selected genes. Results：YSV at 320μg· kg^-1·d^-1 significantly inhibited the growth of transplanted tumor of human hepatocarcinoma BEL-7402 cells in nude mice, with an inhibitory rate of 52.37%. The difference was significant compared with normal saline control group （n=12, P〈0.05）. A total of 781 differential genes were observed after YSV treatment compared with control. Fifty two genes are closely related to the anti-tumor efficacy of YSV, among them 37 tumor proliferation-related genes were down-regulated and 15 tumor suppressor genes were up-regulated. YSV significantly inhibited the expression of oncogene Akt1 and increased the expression of tumor suppressor gene PTEN, which was verified by semiquantitative RT-PCR. Conclusion： YSL exhibits a significant anti-tumor activity by inhibiting the expression of tumor proliferation-related genes and enhancing the expression of tumor suppressor genes to reestablish the balance of them.

关 键 词：肝肿瘤 试验性 抗肿瘤药 酪丝缬肽(YSV) 异种移植模型抗肿瘤试验 基因表达调控 肿瘤 

分 类 号：Q939.91[生物学—微生物学]