环磷酰胺LDM联合MTD化疗对乳腺癌抗血管作用的实验研究

Experimental Study on the Anti-angiogenic Effects of MTD Combined with LDM Cyclophosphamide Chemotherapy for Breast Cancer

目的观察环磷酰胺最大耐受量联合低剂量节律化疗对裸鼠人乳腺癌皮下移植瘤的抗血管生成及促肿瘤细胞凋亡的作用。方法荷瘤裸鼠随机分成4组:LDM组、联合用药组(MTD联合LDM组)、MTD组和对照组。给药21天后,观察各组小鼠瘤质量、瘤体积、白细胞数量,采用免疫组织化学法检测移植瘤MVD、TSP-1表达情况,TUNEL法检测肿瘤细胞凋亡情况。结果联合用药组裸鼠肿瘤的生长速度较其他组明显减慢(P<0.05)。联合用药组裸鼠的肿瘤重量为(0.35±0.03)g,明显轻于其他组(P<0.05)。联合用药组MVD表达水平明显低于MTD组(P<0.05)。联合用药组TSP-1表达水平明显高于MTD组(P<0.05)。联合用药组肿瘤细胞凋亡率明显高于其他组(P<0.05)。结论环磷酰胺MTD联合LDM节律化疗可以抑制乳腺肿瘤的生长速度、血管生成,并促进肿瘤细胞凋亡。

Objective To study the effects of cyclophosphamide（CTX） administered by means of maximum tolerated dose（MTD） combined with low-dose metronomic（LDM） chemotherapy on the anti-angiogenesis and promote apoptosis of breast cancer model.Methods The breast cancer model mice were randomly divided into 4 groups：LDM group,combination group（MTD combined with LDM group）,MTD group,normal sodium control group.Tumor volume and weight and the white blood cell count were observed in the 21st day.The MVD and TSP-1 were detected by immunohistochemistry,and the tumor cell apoptosis was analyzed by TUNEL method.Results The tumor grew significantly slower in the combination group than that in the other groups（P〈0.05）.The tumor weight in the combination group was（0.35± 0.03） g,significantly lower than that in the other groups（P〈0.05）.The expression of MVD in the combination group was significantly decreased compared with MTD group（P〈0.05）.The expression of TSP-1 in the combination group was significantly higher than that in the MTD group（P〈0.05）.The expression of apoptotic index of tumor cells were significantly higher than that in other groups（P〈0.05）.Conclusion CTX administered by means of MTD combined with LDM chemotherapy can inhibit breast tumor growth,tumor angiogenesis and promote tumor cells apoptosis.