节拍化疗通过影响血管形成及免疫系统抑制肿瘤细胞生长的机制

Rhythmic chemotherapy affects the growth of tumor cells by influencing the formation of blood vessels and the immune system

目的研究节拍化疗方案对乳腺癌肿瘤细胞的影响及其作用机制。方法建立荷瘤小鼠模型,给予常规剂量卡培他滨化疗作为常规化疗组,持续低剂量卡培他滨化疗作为节拍化疗组,不应用化疗作为对照组。测定肿瘤血管微密度(Microvessel density,MVD)、血管内皮生长因子(Vascular endothelial growth factor,VEGF)、凝血酶敏感蛋白1(Thrombospondin 1,TSP-1)的表达情况,通过流式细胞仅检测不同化疗方案中骨髓来源抑制性细胞(Myeloid-derived suppressor cells,MDSCs)、NK细胞、巨噬细胞的比例,观察化疗结束后小鼠的肿瘤大小和血中白细胞计数。结果节拍化疗组与常规化疗组比较,MVD、VEGF降低,TSP-1升高,差异有统计学意义(P<0.05)。节拍化疗组与常规化疗组比较,MDSCs比例降低,NK细胞、巨噬细胞的比例升高,差异有统计学意义(P<0.05)。节拍化疗组与常规化疗组在治疗结束后肿瘤体积没有区别(P>0.05),但节拍化疗组小鼠白细胞计数明显高于常规化疗组(P<0.05)。结论持续低剂量卡培他滨化疗通过抑制新生血管形成,调整免疫细胞的比例来抑制肿瘤形成,同时降低化疗引起的副反应,提高生存质量。

Objective The objective of this study was to determine the effect of curative chemotherapy regimen on breast cancer cells and its mechanism.Methods A tumor-bearing mouse model was established and routine dose of capecitabine was given as a conventional chemotherapy group.Continuous low-dose capecitabine chemotherapy was used as a radiotherapy group and no chemotherapy was used as a control group.The expression of microvessel density（MVD）,vascular endothelial growth factor（VEGF）and thrombospondin 1（TSP-1）were measured by flow cytometry.The percentage of myeloid-derived suppressor cells（MDSCs）,NK cells and macrophages in the program was observed.The tumor size and blood leukocyte count were measured after chemotherapy.Results MVD and VEGF in the radiotherapy group were significantly decreased and TSP-1 was significantly increased in comparison with the conventional chemotherapy group（P〈0.05）.The proportion of MDSCs in the radiotherapy group was significantly decreased,the proportion of NK cells and macrophages were significantly increased when compared to the conventional chemotherapy group（P〈0.05）.The tumor volume was no difference between the control and chemotherapy groups（P〉0.05）.However,the white blood cell count in the radiotherapy group was significantly higher than that in the conventional chemotherapy group（P〈0.05）.Conclusion Capecitabine chemotherapy at continuous low-dose inhibits neovascularization and adjusts the proportion of immune cells to suppress tumor formation.Thus,this chemotherapy could reduce side effects caused by chemotherapy and improve the quality of life.