多西他赛联合基质金属蛋白酶抑制剂SB-3CT对前列腺癌移植瘤生长的影响

Effect of Docetaxel plus matrix metalloproteinase inhibitor SB-3CT on the growth of prostate cancer xenografts

目的探讨多西他赛联合基质金属蛋白酶抑制剂(SB-3CT)对前列腺癌移植瘤生长的影响及其可能的作用机制。方法用前列腺癌PC-3细胞建立裸鼠皮下移植瘤模型,随机分为SB-3CT组(注射SB-3CT溶液25 mg/kg),联合用药组(SB-3CT 25 mg/kg+静脉注射多西他赛溶液10 mg/kg)和空白对照组(注射等量生理盐水),每组5只。测量肿瘤体积和质量并绘制生长曲线。免疫组化检测移植瘤组织中PDK1和PFKFB4的表达。结果联合用药组、空白对照组和SB-3CT组平均瘤体质量比较差异有统计学意义(F=29.556,P=0.001),且联合用药组的肿瘤生长速度明显较空白对照组和SB-3CT组慢。免疫组化结果显示,PDK1在联合用药组、空白对照组和SB-3CT组的染色评分分别为(2.33±0.47)分、(6.00±0.81)分和(4.33±0.48)分,组间比较差异有统计学意义(F=18.200,P=0.003),且联合用药组评分低于SB-3CT组(P=0.017);PFKFB4在3组的染色评分分别为(5.33±0.49)分、(11.33±0.47)分和(9.00±1.41)分,组间比较差异有统计学意义(F=17.643,P=0.003),且联合用药组评分低于SB-3CT组(P=0.011)。结论多西他赛联合基质金属蛋白酶抑制剂SB-3CT对前列腺癌移植瘤生长具有抑制作用,糖代谢相关酶PDK1和PFKFB4表达下调可能是潜在的分子机制。

Objective To investigate the effects of Docetaxel plus matrix metalloproteinase inhibitor(SB-3CT)on the growth of prostate cancer xenografts and its possible mechanism. Methods The models of PC3 prostate cancer xenografts were developed based on PC-3 cells in nude mice,which were randomly divided into SB-3CT group(injected with SB-3CT solution 25 mg/kg),combination group(SB-3 T 25 mg/kg+intravenous Docetaxel 10 mg/kg)and blank control group(injected with equal amount of normal saline,with 5 nude mice in each group. The tumor volume and mass were measured,and growth curve were plotted. The expression of PDK1 and PFKFB4 were determined using the immunohistochemical staining. Results The combination group,blank control group and SB-3CT group were statistically significant difference in the average tumor volume(F=29.556,P=0.001),the tumor growth in the combination group was significantly slower than that in the blank control group and the SB-3CT group. The immunohistochemical scores showed that the score of PDK1 in the combination group,the blank control group and the SB-3CT group were 2.33±0.47,6.00±0.81 and 4.33±0.48,respectively,with statistically significant differences(F=18.200,P=0.003),and the score in the combination group was lower than that in the SB-3CT group(P=0.017);the score of PFKFB4 in those three groups were 5.33±0.49,11.33±0.47 and 9.00±1.41,respectively,with statistically significant differences(F=17.643,P=0.003),and the score in the combination group was lower than that in the SB-3CT group(P=0.011). Conclusion Docetaxel plus matrix metalloproteinase inhibitor SB-3CT can inhibit the growth of prostate cancer xenografts,and the down-regulation of glucose metabolism-related enzymes PDK1 and PFKFB4 is a potential mechanism.