促吞噬肽衍生物T肽对裸鼠术后残瘤VEGF表达的影响

Effects of T Peptide on VEGF Expression of Post-Operative Tumors in Nude Mice

目的:探讨促吞噬肽衍生物T肽抑制裸鼠术后残瘤生长的作用机理。方法:建立MCF-7乳腺癌裸鼠皮下移植瘤术后残瘤模型,观察8 mg/kg剂量T肽对残余肿瘤组织的生长情况,并采用免疫组化和Western印迹检测给药后残瘤组织血管内皮生长因子(VEGF)的表达,采用RT-PCR检测不同T肽浓度对血管内皮细胞VEGF基因转录的影响。结果:T肽对MCF-7乳腺癌裸鼠皮下移植瘤术后残瘤生长表现出良好的抑制作用,按照瘤重得出的抑制率为68.2%,按照肿瘤体积得出的抑制率为67.6%,T肽给药组裸鼠残瘤组织中VEGF的表达量较空白对照组明显减少。血管内皮细胞中T肽呈剂量相关性抑制VEGF基因的转录。结论:T肽的抗癌作用与其抑制肿瘤微环境肿瘤组织和血管内皮细胞中VEGF的表达有密切联系,预示着T肽有潜力成为预防术后残瘤生长的抗癌新药。

Objective： To study the possible inhibition mechanisms of T peptide derived from tuftsin on growth of residual tumors in nude mice after surgery. Methods： The nude mice were implanted breast tumor cell line MCF-7 to allow the tumor to grow, and then they were operated to prepare the mice models with residual tumor. The inhibitory effect of T peptide on post-operative tumors was studied by measuring the tumor tissues size of the mice model receiving 8 mg/kg T peptide every 2 days for 10 days. And expression of vascular endothelial growth factor（VEGF） was detected in these tumor tissues by Western blot and immunohistochemistry. The VEGF gene transcriptions in human umbilical vein endothelial cells（HUVEC） treated by different concentration T peptide were detected by RT-PCR. Results： In post-surgical residual tumors, T peptide produced strong inhibitory effect with tumor weight suppression rate of 68.2% and tumor volume inhibition rate of 67.6%. The protein expression of VEGF in residual tumor tissues of T peptide group was significantly lower than that of control group. The mRNA level of VEGF in HUVEC in vitro decreased by T peptide with a dose-dependent manner. Conclusion： Inhibiting the expression of VEGF in tumor is the mechanism of antitumor effects on the post-surgical residual tumors in mice by T peptide. So T peptide might be a promising candidate drug for the remedy for post-surgical residual tu-