结肠癌中氨磷汀对顺铂的增敏作用及其肾脏的保护作用

Effect of amifostine on sensitization to cisplatin and renal protection in colon cancer

目的研究结肠癌中氨磷汀对顺铂的增敏作用及其肾脏保护作用。方法用0,0.02,0.04,0.08,0.16 mg/L的顺铂分别与0,100,200,800 mg/L的氨磷汀联合处理CMT93和SW620细胞,用CCK-8检测细胞活性,用Bliss法计算两药联合指数。构建裸鼠皮下移植瘤模型,分为对照组、顺铂组、氨磷汀组和氨磷汀联合顺铂组,绘制各组移植瘤的生长曲线,测量各组移植瘤的体积和质量,检测各组小鼠的肾脏指数、血清肌酐及尿素氮水平。结果氨磷汀和顺铂协同抑制SW620和CMT93细胞的增殖,两药联合指数分别为25.698(SW620细胞)和27.65(CMT93细胞)。顺铂组和联合组移植瘤质量和体积小于对照组,差异具有统计学意义(P<0.05);联合组移植瘤质量与体积小于顺铂组,差异具有统计学意义(P<0.05);顺铂组小鼠的肾脏指数、尿素氮和肌酐水平显著高于其他各组(P<0.05),而联合组、氨磷汀组与对照组间差异无统计学意义。结论氨磷汀在体内外增加结肠癌细胞对顺铂的敏感性,并有效地改善顺铂引发的肾功能损伤。

Objective To study the effect of amifostine on cisplatin sensitization and renal protection in colon cancer.Methods CMT93 cells and SW620 cells were treated with 0,0.02,0.04,0.08,0.16 mg/L cisplatin combined with 0,100,200,800 mg/L amifostine,respectively.The cell activity was detected by CCK-8,and the combination index was calculated by Bliss method.The nude mouse models of subcutaneous transplantation tumor were established and divided into control group,cisplatin group,amifostine group and amifostine combined with cisplatin group.The growth curves of transplanted tumor were drawn in each group,the volume and the mass of transplanted tumor were measured,and the kidney index and the levels of serum creatinine and urea nitrogen were detected.Results Amifostine and cisplatin synergistically inhibited the proliferation of SW620 and CMT93 cells,and the synergy score was 25.698 in SW620 cells and 27.65 in CMT93 cells,respectively.The growth rate of transplanted tumor in cisplatin group and combination group was slower than that in control group,and the mass and the volume were statistically lower than those in control group(P<0.05).The growth rate of transplanted tumor in combination group was slower than that in cisplatin group,and the mass and the volume were significantly lower than that in cisplatin group(P<0.05).The kidney index and the levels of urea nitrogen and creatinine in cisplatin group were significantly higher than those in the other groups(P<0.05),and there was no significant difference between combined group,amifostine group and control group.Conclusion Amifostine can increase the sensitivity of colon cancer cells to cisplatin,enhance the antitumor effect of cisplatin in mice colon cancer,and effectively improve the renal function damage caused by cisplatin.