伊立替康节拍式化疗联合索拉非尼对小鼠移植性肝癌的作用

Effects of metronomic irinotecan chemotherpy combined with sorafenib on hepatocellular carcinoma mice model

关键词:  肝癌  索拉非尼  伊立替康  节拍式化疗

Key words:  hepatocellular carcinoma  sorafenib  irinotecan  metronomic chemotherpy

摘要:

[目的] 观察伊立替康(CPT-11)节拍式化疗联合索拉非尼(Sorafenib)对小鼠移植瘤生长的抑制作用及对血管增殖的影响。[方法] 建立小鼠HCa肝癌移植瘤模型后，将荷瘤小鼠随机分成5组：空白对照组(A组)；Sorafenib组(B组)；CPT-11节拍式给药(LDM)组(C组)；CPT-11常规剂量(TDM)组(D组)； Sorafenib + CPT-11(LDM)组(E组)。用药28 d停药，24 h后处死小鼠，测量瘤体积及瘤重，计算抑瘤率，并用免疫组化SP法测定肿瘤细胞中VEGF表达和间质细胞CD31的表达，以计算微血管密度（MVD）。[结果] 索拉非尼、CPT-11对小鼠HCa肝癌的生长均有抑制作用，E组抑瘤率(0.5490%)明显高于其他3个实验组(P<0.05)；而且E组肿瘤细胞中VEGF表达明显降低、MVD计数明显减少(P<0.05)。[结论] CPT-11节拍式化疗联合索拉非尼可协同抑制小鼠HCa肝癌移植瘤生长及血管形成，节拍式化疗联合分子靶向治疗可能成为肝癌综合治疗的新途径。

Abstract:

[Objective] To observe the inhibition effect of low dose CPT-11 combined with sorafenib on the growth of tumors and the vascular proliferation in mice. [Methods] mouse tumor model was set up by implanting murine ascites hepatocarcinoma cell (HCa) subcutaneous in mice．Seventy-five experimental mice were randomly divided into 5 groups：control group(A)， sorafenib-treated group(B)，CPT-11(LDM)-treated group(C)，CPT-11(TDM)-treated group(D) and combination-treated group(E). The mice were treated for 28 days，and then terminated. The volume and weitht of tumors were recorded. The expressions of vascular endothecial growth factor (VEGF) and CD31 were detected by immunohistochemistry. Moreover，the micro-vessel density (MVD) was calculated according to the expression of CD31. [Results] Both sorafenib and low dose CPT-11 can inhibite the growth of tumors. The inhibition of group E was higher than other 3 treated groups (P<0.05) .And so was the expression of VEGF and MVD (P<0.05)．[Conclusion] Metronomic CPT-11 chemotherpy combined with Sorafenib have significant inhibitory effect on the growth of tumors and the expression of the VEGF and MVD in HCa liver cancer tumor—bearing mice．Metronomic chemotherpy combined with molecularly targeted therapy may be a new way of anti-tumors.