二甲双胍联合柔红霉素对人结肠癌细胞裸鼠移植瘤的影响

Effect of Metformin Combined with Daunorubicin on Human Colon Cancer Cell Line in Nude Mice

目的探讨二甲双胍联合柔红霉素对人结肠癌细胞SW480裸鼠移植瘤的影响。方法体外培养人结肠癌细胞SW480,建立结肠癌动物模型。将40只荷瘤裸鼠,随机分为4组:模型组(0.9%氯化钠注射液),二甲双胍组(100mg·kg-1),柔红霉素组(0.1 mg·kg-1),二甲双胍组与柔红霉素合用组(100 mg·kg-1+0.1 mg·kg-1)。进行药物干预后,绘制肿瘤生长曲线,处死裸鼠后,称量瘤体质量,计算抑瘤率,应用HE染色观察结肠癌细胞的增殖情况,TUNEL试剂盒检测肿瘤细胞的凋亡情况。结果与其他组比,两药合用组的瘤体积小、生长缓慢。瘤体湿重结果显示,合用组与模型组比较有显著性差异(P<0.05)。二甲双胍组、柔红霉素组及合用组抑瘤率分别是19.30%、28.51%、64.04%。HE染色结果表明,在蓝色深染区为肿瘤细胞,其中合用组蓝色深染区减少最明显。TUNEL检测显示,模型组与其他组相比凋亡细胞数目最少,而合用组细胞凋亡的数目最多。结论二甲双胍联合柔红霉素能够有效抑制裸鼠结肠癌细胞的生长,其可能的作用机制与诱导结肠癌细胞的凋亡有关。

Objective To investigate the effect of metformin combined with daunorubicin on human colon cancer cell line（ SW480） in nude mice. Methods Human colon cancer cells（ SW480） were cultured in vitro to establish an animal model of colon cancer. 40 tumor-burdened nude mices were randomly divided into 4 groups： model group（ 0. 9%saline）,metformin group（ 100 mg·kg^-1）,daunorubicin group（ 0.1 mg·kg^-1）,and metformin combined with daunorubicin group（ 100 mg·kg^-1＋ 0. 1 mg·kg^-1）. After drug intervention,the growth curve of tumor was drawn. The mice were sacrificed to weigh the tumor and calculate the inhibitory rate before HE staining was used to observe the proliferation of colon cancer cells. TUNEL kit was used for detection of tumor cell apoptosis. Results In the combined group,tumors grew more slowly than in other groups,but the volume was smaller. According to the results of wet weight of tumors,there was significant difference between the combined group compared and model group（ P〈0.05）. The inhibitory rate of the metformin group,the daunorubicin group and combined group was 19. 30%,28. 51%,64. 04%,respectively. According to TUNEL detection,the combined group had the largest number of apoptosis cells. Conclusion Metformin combined with daunorubicin can effectively inhibit the growth of colon cancer cells in nude mice. The mechanism may be associated with the induction of apoptosis of colon cancer cells.