常规化疗联合节律性化疗对荷骨肉瘤SD大鼠的治疗效应  

Therapeutic effect of metronomic chemotherapy combined with conventional chemotherapy on osteosarcoma in SD rats

作　　者：祝晓忠[1] 梅炯[1] 毕刚[1] 陈雁西[1] 林娜[1] 

机构地区：[1]同济大学附属同济医院骨科,上海200065

出　　处：《肿瘤》2010年第9期758-762,共5页Tumor

摘　　要：目的:观察常规化疗联合节律性化疗方案对荷骨肉瘤SD大鼠移植瘤的抑制效应,并比较不同化疗方案的效应。方法:将110只荷骨肉瘤SD大鼠随机分成4组,其中3组分别采用常规化疗、节律性化疗以及常规化疗联合节律性化疗予以处理,另一组留作空白对照不作任何治疗处理。治疗期间,每周测量肿瘤大小;8周治疗结束后,处死SD大鼠,取出肿瘤并称取瘤体质量。应用Western印迹法对移植瘤组织中血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)蛋白的表达水平进行半定量分析。结果:3种化疗方案均可抑制骨肉瘤移植瘤在SD大鼠体内的生长。常规化疗组和节律性化疗组的移植瘤生长曲线相似;但在化疗后期,这2种化疗方案均失去对肿瘤的抑制作用,而常规化疗联合节律性化疗始终保持抑瘤作用。化疗8周后,对照组与常规化疗组、节律性化疗组以及常规化疗联合节律性化疗组之间的移植瘤质量和体积差异均有统计学意义(P<0.01);常规化疗联合节律性化疗组与其他2个化疗组的移植瘤质量和体积差异也有统计学意义(P<0.01)。常规化疗联合节律性化疗组的抑瘤作用最为明显。Western印迹法结果显示,各化疗组移植瘤组织中VEGFA的相对表达水平均较对照组有所下调(P<0.01);节律性化疗组和常规化疗联合节律性化疗组移植瘤组织中VEGFA的相对表达水平明显低于常规化疗组。结论:常规化疗联合节律性化疗具有抗血管生成效应,抑瘤作用最为明显,有望成为一种有效的骨肉瘤治疗方案。Objective:To investigate the inhibitory effects of conventional chemotherapy combined with metronomic chemotherapy on the growth of xenografted osteosarcoma in SD rats and compare the efficacy between different therapeutic regimens.Methods:One hundred and ten SD rats bearing osteosarcoma were divided into 4 groups randomly.Three groups were given conventional,metronomic,and combined chemotherapies while the forth group was as a control group.The tumor volumes were measured every week during the treatment period.At the end of 8-week treatment,the rats were sacrificed and the isolated tumors were weighed.Expression of vascular endothelial growth factor A(VEGFA) protein in tumors was determined by Western blot assays.Results:The three therapeutic regimens had inhibitory effects on the growth of osteosarcoma in SD rats.Conventional and metronomic chemotherapies had similar effects on tumor growth but both of them lost their inhibitory effect in the late period.However the combination therapy maintained the effectiveness till the end of the treatment.The tumor volumes and weights in the three treatment groups had statistically significant difference with control group at the 8th week after chemotherapy(P<0.01).There was significant difference in tumor volume and weight between combination treatment group and conventional chemotherapy group and between combination treatment group and metronomic chemotherapy group(P<0.01).Combination therapy achieved most powerful inhibitory effects on the growth of osteosarcoma(P<0.001).Western blot indicated that the expression of VEGFA decreased significantly in all the treatment groups(P<0.01) and the combination therapy group had the lowest VEGFA expression.Conclusion:Conventional chemotherapy combined with metronomic chemotherapy has more powerful anti-angiogenesis and anti-tumor effects.It will become an effective therapeutic regimen for osteosarcoma.

关 键 词：骨肉瘤 节律性化疗 新辅助化疗 动物实验 

分 类 号：R73[医药卫生—肿瘤]