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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
【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.
【Key words】 Liver neoplasms,experiment; Antineoplastic agents; Tyroservaltide(YSV); Xenograft model antitumor assays; Gene expression regulation,neoplastic;
- 【文献出处】 肿瘤 ,Tumor , 编辑部邮箱 ,2006年08期
- 【分类号】R735.7
- 【被引频次】6
- 【下载频次】116