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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: To investigate the chemosensitivity of cyclophilin A (cyclosporine A, Cs A) and cisplatin (CDP) to improve the sensitivity of lung cancer cells to DDP. Methods: C57BL / 6 nude mice were randomly divided into 4 groups: blank control group, DDP group, CsA group and combined group (DDP + Cs A), 10 in each group. The nude mice were injected subcutaneously with 100μl mouse Lewis lung carcinoma cell line (3LL) cell suspension with a density of 5 × 106 / ml on the left axilla of nude mice. After 2 days of inoculation, intraperitoneal injection of DLL was given intraperitoneally. The dose of DDP was 2 mg / kg, Once every 3 days, a total of 3 times; Cs A dose of 5 mg / kg, every other day, a total of 3 times; thereafter experimental group once a week to maintain plasma concentration. Blank control group is not given. The tumor growth was observed every 3 days after inoculation and the tumor growth curve was drawn. The nude mice were sacrificed 35 days after inoculation and the tumor masses were removed. The histological changes were observed by H-E staining and the expression of Ki-67 protein in the xenografts was observed by immunohistochemistry. Results: The nude mice in the combination group had significantly lower tumor volume (P <0.01), tumor weight (P <0.05), tumor cell density (P <0.05) and mitosis (P <0.05) The tumor volume, tumor mass, tumor cell density and mitosis in nude mice in CsA group were lower than those in blank control group (all P <0.05). Immunohistochemistry showed that the expression of Ki-67 in the xenografts in the combined group was significantly decreased. Conclusion: The combination of immunosuppressant Cs A and DDP can improve the sensitivity of lung cancer cells to DDP and synergistically inhibit the growth of lung cancer xenografts.