摘要目的:观察重组肿瘤抑素T42肽对人肝癌干细胞(liver cancer stem cells，LCSCs)体外血管生成及小鼠体内荷瘤能力的影响。方法:培养人肝癌细胞系SMMC-7721，免疫磁珠法提取富集CD133 + (Cluster of Differentiation 133)肝癌干细胞LCSCs；构建稳定表达的LCSCs-Luc细胞系；人工合成T42肽。将LCSCs分为对照组、T42肽处理组和5-氟尿嘧啶组。体外血管形成实验检测3组LCSCs处理24 h后的成血管能力；建立免疫缺陷小鼠(中国科学院动物研究所)移植瘤模型( n＝9)，小动物活体成像检测成瘤能力；将9只成瘤小鼠分为3组( n＝3)，隔日注射生理盐水、T42肽(40 mmol/L)和5-氟尿嘧啶(40 mmol/L)，共注射7次，14 d后小动物活体成像检测3组小鼠的治疗作用。并记录瘤体体积变化。两组间比较予以 t检验，不符合正态分布的予以单因素方差分析。 结果:与对照组比较，T42肽、5-氟尿嘧啶处理组LCSCs的体外血管生成数[(3.51±1.64)、(4.53±2.17)个]显著低于对照组[(11.50±2.07)个]，差异有统计学意义( t＝11.112、8.978， P<0.05)。T42肽、5-氟尿嘧啶处理4周后，小鼠LCSCs异位荷瘤的瘤体的光子通量[(1.53±0.35)×10 6光子/s/cm 2、(1.87±0.31)×10 6光子/s/cm 2]显著低于对照组[(4.23±0.15)×10 6光子/s/cm 2]，差异有统计学意义( t＝12.213、12.004， P<0.05)。 结论:T42肽对LCSCs的体外血管生成能力及动物体内成瘤能力均有较强的抑制作用。

abstractsObjective:To investigate the effect of recombinant tumor suppressor T42 peptide on angiogenesis and tumorigenicity of human liver cancer stem cells (LCSCs).Methods:The LCSCs enriched with CD133 + liver cancer stem cells were extracted by immunomagnetic bead method from the human hepatoma cell line SMMC-7721. The stable expression of LCSCs-Luc cell line was constructed. T42 peptide was synthesized artificially; and LCSCs were divided into control group, T42 peptide treatment group and 5-fluorouracil group. The angiogenesis ability of LCSCs was detected by in vitro angiogenesis test. The therapeutic effect of different treatments on tumor bearing mice was detected by small animal imaging. Two-tailed Student′s t-test was adopted to analyze the significance between two independent groups. One-way ANOVA was used to compare differences between multiple groups. Results:As compared with the control group (11.50±2.07), the number of in vitro angiogenesis of LCSCs in T42 peptide and 5-fluorouracil groups (3.51±1.64, 4.53±2.17) was significantly reduced ( t=11.112, 8.978, P<0.05). After treatment with T42 peptide and 5-fluorouracil for 4 weeks, the photon flux of ectopic tumor bearing mice [(1.53±0.35)×10 6 photons/S/cm 2, (1.87±0.31)×10 6 photons/S/cm 2] was significantly lower than that in the control group [(4.23±0.15)×10 6 photons/S/cm 2, t=12.213, 12.004, P<0.05]. Conclusion:T42 peptide can inhibit the angiogenesis and reduce the tumorigenicity of LCSCs.