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目的:研究最大耐受剂量(MTD)化疗间歇期给予节律低剂量CTX对人乳腺癌裸鼠移植瘤的作用。方法:建立人乳腺癌裸鼠移植瘤模型,随机分为小剂量节律(LDM)组、最大耐受剂量(MTD)组、最大耐受剂量联合节律(MTD+LDM)组和生理盐水对照组,治疗21d为1个周期。测量瘤体积、裸鼠体质量及外周血白细胞计数。处死裸鼠后测量瘤质量,应用免疫组化方法检测瘤组织中血管内皮生长因子(VEGF)、微血管密度(MVD)及增殖细胞核抗原(PCNA)的表达。结果:各治疗组均抑制了肿瘤生长;联合组瘤质量及21d时肿瘤体积与其他各组相比均显著降低,P<0.05。联合组抑瘤率为69.15%,与对照组及MTD组相比,联合组和LDM组肿瘤组织的VEGF水平及MVD值显著降低,P<0.05;与LDM组和对照组相比,联合组和MTD组肿瘤组织PCNA表达水平均显著降低,P<0.05。各治疗组裸鼠体质量及白细胞计数差异无统计学意义,P>0.05。结论:最大耐受剂量间歇期给予节律低剂量CTX通过同时抑制肿瘤细胞增殖活性和肿瘤血管生成,在未增加毒副反应的前提下抑瘤效果更好,为可行有效的方案。
Objective: To study the effect of low-dose rhythmic CTX on human breast cancer xenografts in nude mice during intermittent MTT chemotherapy. Methods: The model of human breast cancer xenografts in nude mice was established and randomly divided into low dose rhythm (LDM) group, maximum tolerated dose (MTD) group, MTD + LDM group and saline control group, Treatment for 21d for a cycle. Measurement of tumor volume, nude mice body mass and peripheral white blood cell count. The tumor weight was measured after the nude mice were sacrificed. The expression of vascular endothelial growth factor (VEGF), microvessel density (MVD) and proliferating cell nuclear antigen (PCNA) were detected by immunohistochemistry. Results: The tumor growth was inhibited in all treatment groups. The tumor mass in combination group and the tumor volume at 21 d were significantly lower than those in other groups (P <0.05). The combined tumor inhibition rate was 69.15%. Compared with the control group and the MTD group, the VEGF and MVD in the combined group and the LDM group were significantly decreased (P <0.05). Compared with the LDM group and the control group, the combined group and the control group The expression level of PCNA in MTD group was significantly decreased, P <0.05. There was no significant difference in body weight and white blood cell count between nude mice in each treatment group (P> 0.05). Conclusions: Intermittent maximal tolerated dose of rhythmic low dose CTX can be a viable and effective regimen by inhibiting tumor cell proliferation activity and tumor angiogenesis at the same time without any side effects.