环孢菌素A联合顺铂对Lewis肺癌裸鼠移植瘤的协同抑制作用  

Synergistic inhibition effects of cyclosporin A and cisplatin against lung cancer: a pilot study in nude mice

作　　者：朱新海[1] 郭良君[1] 

机构地区：[1]暨南大学附属第一医院肿瘤科,广东广州510632

出　　处：《中国肿瘤生物治疗杂志》2015年第5期607-611,共5页Chinese Journal of Cancer Biotherapy

摘　　要：目的:探讨亲环蛋白A(cyclophiline A,Cy PA)抑制剂环孢菌素A(cyclosporine A,Cs A)联合顺铂(Cisplatin,DDP)化疗提高肺癌细胞对DDP的敏感性。方法:C57BL/6裸鼠随机分为4组:空白对照组、DDP组、Cs A组和联合组(DDP+Cs A),每组各10只。裸鼠左侧腋部皮下注射100μl细胞密度为5×106/ml的小鼠Lewis肺癌细胞株(3LL)细胞悬液,接种2 d后开始腹腔给药,DDP给药剂量为2 mg/kg,每3 d 1次,共3次;Cs A给药剂量5 mg/kg,隔天1次,共3次;此后实验组每周1次,维持血药浓度。空白对照组不给药。接种后每3天观察一次肿瘤生长情况,绘制肿瘤生长曲线。接种35 d后处死裸鼠取出瘤块,H-E染色观察组织形态学变化,免疫组化法观察移植瘤中Ki-67蛋白的表达情况。结果:联合组裸鼠的移植瘤体积(P<0.01)、移植瘤质量(P<0.05)、肿瘤细胞密度(P<0.05)、核分裂象(P<0.05)均较其余3组显著降低;DDP组和Cs A组裸鼠移植瘤体积、瘤质量、肿瘤细胞密度和核分裂象均较空白对照组低(均P<0.05)。免疫组化观察联合组移植瘤组织的Ki-67表达水平明显降低。结论:免疫抑制剂Cs A与DDP联合用药可提高肺癌细胞对DDP的敏感性,协同抑制肺癌细胞移植瘤的生长。Objective: The purpose of this study was to evaluate the effect of cyclosporine A( Cs A) plus cisplatin( DDP) on lung cancer growth in vivo. Methods: Lewis lung carcinoma 3LL cells( 100 μl of 5 × 106/ ml) were injected subcutaneously into female nude( C57 BL /6) mice. Two days after xenograft injection,animals were randomized to four treatment groups( n = 10) : Control,cisplatin( DDP),cyclosporine A( Cs A),and DDP + Cs A. DDP and Cs A were intraperitoneally administered initially at 2 mg / kg,q3 d for 3 times and at 5 mg / kg,q2 d for 3 times,respectively,and once a week afterwards. Tumor size was examined every three days. The weight of tumor mass was calculated. Animals were sacrificed 35 days after xenograft implantation. Tumors were collected and weighed. Tumor tissue specimens were subjected to H-E staining immunohistochemical assessment of Ki-67 expression. Results: Compared with the control,all drug treatments significantly reduced tumor size( P < 0. 01),tumor weight( P < 0. 05),cell density and mitotic count( P <0. 05) and Ki-67 expression( P < 0. 05),but DDP together with Cs A was significantly more effective than DDP and Cs A each alone( P < 0. 05). Conclusion: The combined use of Cs A and DDP may increase the sensitivity of lung carcinoma cells to DDP and thus have a synergistic effect against lung cancer.

关 键 词：环孢菌素A(Cs A) 顺铂(DDP) 肺癌 移植瘤模型 

分 类 号：R734.2[医药卫生—肿瘤]