bFGF单抗协同替吉奥抑制肺癌Lewis细胞的增殖及移植瘤血管新生

Synergistic inhibitory effects of bFGF monoclonal antibody and S-1 against proliferation of lung cancer Lewis cells and angiogenesis of transplanted tumors

目的:探讨碱性成纤维生长因子(basic fibroblast growth factor,bFGF)单抗与替吉奥(gimeracil and oteracil porassi-um,又称S-1)联合应用体内外抑制小鼠Lewis肺癌细胞增殖、移植瘤生长及转移、肿瘤血管新生的协同作用。方法:CCK-8法检测bFGF单抗及S-1对Lewis细胞增殖的抑制作用。建立C57BL/6小鼠Lewis肺癌自发转移瘤模型,32只小鼠随机分成生理盐水(NS)组、bFGF单抗组、S-1组和bFGF单抗+S-1组,每组8只;测量瘤体,绘制生长曲线,称瘤质量并计算抑瘤率;计数各组肺表面转移瘤结节;CD31标记血管内皮细胞,计数转移瘤微血管密度(microvessel density,MVD)。结果:bFGF单抗、S-1剂量依赖性抑制Lewis细胞增殖(P<0.05),联合用药组抑制率明显高于单药组(P<0.05或P<0.01)。bFGF单抗组、S-1组以及bFGF单抗+S-1组对Lewis转移瘤的抑瘤率分别为37.8%、47.7%、65.9%,联合组抑瘤率明显高于单药组(P<0.05或P<0.01)。联合组肺表面转移结节、微血管密度明显低于单药组(2.71±0.76vs6.57±0.98、4.71±0.76;21.6±2.9vs33.4±4.9、41.9±6.3;P<0.05或P<0.01)。结论:bFGF单抗联合S-1对Lewis肺癌移植瘤具有协同抑制作用,其机制与抑制细胞增殖及血管新生有关。

Objective： To study the synergistic inhibitory effects of basic fibroblast growth factor（bFGF） monoclonal antibody（bFGF mAb） and gimeracil and oteracil porassium（S-1） against proliferation of Lewis cells and the growth,metastasis,angiogenesis of the transplanted tumors.Methods： CCK-8 assay was used to assess the effects of bFGF mAb and S-1 on proliferation of Lewis cells.The spontaneous Lewis cell lung metastatic model was established,and thirty-two C57BL /6 mice were randomly divided into 4 groups： normal sodium（NS） group,bFGF mAb group,S-1 group,and bFGF mAb＋S-1 group.Tumor volume was measured and tumor growth curve was drawn;tumors were weighed and the inhibitory rate of tumor growth was calculated;metastatic nodules on lung surface were counted;and the vascular endothelial cells were stained with CD31 to examine the microvessel density（MVD） of transplanted tumors.Results： Both bFGF mAb and S-1 inhibited Lewis cell proliferation in a dose-dependent manner（P〈0.05）.The inhibitory rate in bFGF mAb＋S-1 group was significantly higher than those in the single drug treatment groups（P〈0.05 or P〈0.01）.The inhibitory rates of transplanted tumors in bFGF mAb group,S-1 group,and bFGF mAb＋S-1 groups were 37.8%,47.7%,and 65.9%,respectively,with the combination group being significantly higher than the single treatment groups（P〈0.05 or P〈0.01）.Moreover,the metastatic nodules and MVD in the combination group were significantly lower than those of single treatment groups（2.71±0.76 vs 6.57±0.98,4.71±0.76;21.6±2.9 vs 33.4±4.9,41.9±6.3;P〈0.05 or P〈0.01）.Conclusion： bFGF mAb and S-1 have synergistic inhibitory effects on Lewis transplanted tumors,which is related to the inhibition of proliferation and angiogenesis.