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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 antitumor effect of small molecule tripeptide tyroservatide (YSV) and analyze the effect of YSV on the gene expression of tumor cells. Methods: The human hepatocellular carcinoma BEL-7402 xenografted nude mice model was established. The gene expression of YSV in human hepatoma BEL-7402 xenografted tumor was analyzed by gene chip technology. The expression of related genes was verified by RT-PCR. Results: YSV significantly inhibited the growth of human hepatoma BEL-7402 xenografts in nude mice at the dose of 320 μg · kg -1 d -1, with a tumor inhibition rate of 52.37%. Compared with the saline group Comparison was statistically significant (P <0.05). There were 781 genes in YSV group compared with saline group. Among them, 52 genes were closely related to antitumor effect, 37 were down-regulated in gene expression and 15 were up-regulated in tumor growth inhibition. The result of RT-PCR confirmed that YSV could obviously inhibit the oncogene Akt of tumor cells and up-regulate the expression of tumor suppressor gene PTEN. CONCLUSION: YSV has significant anti-tumor activity, which can inhibit the expression of genes related to tumor proliferation and enhance the expression of genes related to tumor growth inhibition in order to restore the balance between them and achieve anti-tumor cell effect.