苦参碱对CT26荷瘤小鼠肿瘤组织中VEGF及HIF-1α水平的影响

Anti-tumor effects of matrine on colon tumor-bearing mice and the expression of VEGF and HIF-1α in tumor

关键词:  苦参碱  结肠癌荷瘤小鼠  血管内皮生长因子  缺氧诱导因子-1α

Key words:  matrine  colon tumor-bearing mice  VEGF  HIF-1α

摘要:

[目的] 研究苦参碱对CT26荷瘤小鼠肿瘤组织中血管生成的影响及相关作用机制。[方法] 通过建立CT26荷瘤小鼠模型，随机分为模型组、阳性药组、苦参碱低剂量组、苦参碱中剂量组、苦参碱高剂量组，造模后分别灌胃生理盐水，环磷酰胺和不同剂量的苦参碱，连续灌胃14 d，检测给药后各组小鼠肿瘤大小，计算抑瘤率，并进行肿瘤组织苏木精-伊红（HE）染色，考察苦参碱对荷瘤小鼠的治疗作用。此外通过实时荧光定量聚合酶链反应（qPCR）及免疫组化法检测各组小鼠肿瘤组织中血管内皮生长因子（VEGF）、缺氧诱导因子-1α（HIF-1α）的表达，初步探究其作用机制。[结果] 造模给药后，与模型组相比，阳性药组和苦参碱低、中、高剂量组小鼠肿瘤重量均显著降低（P<0.01）。HE染色结果表明，模型组肿瘤组织中可见大量核分裂象，无明显坏死区，而阳性药组和苦参碱低、中、高剂量组肿瘤组织中核分裂象显著减少（P<0.01），且细胞坏死更为严重。此外，qPCR结果表明，与模型组相比，阳性药组和苦参碱低、中、高剂量组肿瘤组织中VEGF、HIF-1αmRNA表达水平均显著下调（P<0.05）。各实验组免疫组化结果表明，阳性药组和苦参碱低、中、高剂量组肿瘤组织中VEGF、HIF-1α的积分光密度值（IOD）较模型组显著下调（P<0.05）。[结论] 苦参碱可能是通过降低肿瘤组织中VEGF、HIF-1α的表达水平达到抑制CT26荷瘤小鼠移植瘤生长的作用。

Abstract:

[Objective] The aim of this study is to investigate the effects of matrine on colon tumor-bearing mouse model. In addition,the anti-tumor mechanism of matrine is studied based on inhibiting blood vascular development.[Methods] CT26 tumor cells were injected into mice to induce tumor xenograft animal models. The tumor-bearing mice were devided into Model,Positive Control,Low-dose matrine,Middle-dose matrine and High-dose matrine groups respectively. After CT26 cell injection,mice in each group were orally treated with normal saline,cyclophosphamide and different dosages of matrine respectively. The tumors were weighed and stained with HE to study the anti-tumor effects of materine on colon tumor-bearing mice. Moreover,qPCR and immunostaining were performed to investigate the expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α (HIF-1α) in tumor.[Results] Results indicated a significant anti-tumor effects of matrine reflecting on a remarkable tumor inhibition rate and increased necrosis and nucleolysis of tumor cells. Moreover,matrine could decrease the expression of VEGF and HIF-1α on both gene and protein levels in the tumor.[Conclusion] Matrine could inhibite tumor growth in colon tumor-bearing mice. The anti-tumor mechanisms of matrine maybe through regulating VEGF and HIF-1α expression.