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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

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【作者】 王松; 陆融; 朱智彤; 赵茜; 卢奕; 贾静; 傅正; 周春雷; 赵岚; 李会强; 李鸿钊; 姚智;

【Author】 WANG Song~1 LU Rong~(1,2) ZHU Zhi-tong~1 ZHAO Qian~1 LU Yi~1 JIA Jing~1 FU Zheng~1 ZHOU Chun-lei~1 ZHAO Lan~1 LI Hui-qiang~1 LI Hong-zhao~1 YAO Zhi~(1*) (1.Department of Immunology,Tianjin Medical University,Tianjin 300070,China;2.Pharmaped Research & Development (Shenzhen) Limited,Shenzhen 518029,China)

【机构】 天津医科大学免疫学教研室; 天津医科大学免疫学教研室 天津300070; 天津300070一泰医药研究(深圳)有限公司; 深圳518029; 天津300070;

【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。

【Abstract】 Objective:To observe the anti-tumor effects of a bioactive tripeptide,tyroservahide (YSV),and analyze its in- fluence on gene expression profile of tumor cells.Methods:Transplanted tumor model was established by implanting human hepa- tocarcinoma BEL-7402 cells into nude mice.Gene expression profile in the tumor cells was assayed by gene-chip analysis.Semi- quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to verify the result of the selected genes.Re- sults: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 ex- pression of tumor suppressor gene PTEN,which was verified by semiquantitative RT-PCR.Conclusion:YSL exhibits a signifi- cant 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.

【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)
  • 【分类号】R735.7
  • 【被引频次】6
  • 【下载频次】116
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