氟尿嘧啶联合CIK细胞在小鼠结肠癌模型中抗肿瘤效应的研究

Experimental study on the anti-tumor effect about fluorouracil and cytokine-induced killer(CIK)cells combination on colon Cancer in a mouse syngeneic model

探讨氟尿嘧啶(5-FU)、CIK细胞以及5-FU联合CIK细胞对小鼠结肠癌移植瘤生长的作用,为临床上联合应用5-FU和CIK细胞治疗结肠癌提供理论依据。建立BALB/C小鼠结肠癌模型,在体外诱导培养小鼠CIK细胞,5-FU(12.5mg/kg,d0)联合CIK细胞(1×107,d3)处理小鼠结肠癌荷瘤模型,并绘制肿瘤生长曲线,生存分析采用Kaplan-Meier法及logrank检验,应用流式细胞仪分析荷瘤鼠肿瘤组织中淋巴细胞CTLA-4和非淋巴细胞CD80、CD86表达;RT-PCR法检测肿瘤组织中IFN-γ和TNF-α表达量。5-FU联合CIK细胞治疗组小鼠肿瘤生长速度明显慢于单治疗组,差异有统计学意义(P<0.05);5-FU处理后小鼠移植瘤组织中CD45+细胞表面CTLA-4表达量提高,且CD45-细胞CD80和CD86表达量增加;5-FU联合CIK细胞治疗可提高肿瘤组织IFN-γ与TNF-α表达量,且联合治疗组与单治疗组中IFN-γ的表达量之间的差异有统计学意义(P<0.05)。5-FU联合CIK细胞治疗对结肠癌移植瘤生长的抑制作用大于单独应用5-FU或CIK细胞,且可提高BALB/C小鼠结肠癌模型免疫功能。

To investigate the anti-tumor effects of cytokine-induced killer（CIK）cells combined with fluorouracil on colon cancer in a mouse syngeneic model,BALB/C mouse colon cancer models were established.Murine CIK cells were expanded in vitro;mouse were treated with 5-fluorouracil（5-FU）（12.5mg/kg,D0）and CIK cells（1×107,D3）,and the tumor growth was observed and the tumor growth curve was drawn.The survival data of the treatment was analyzed using Kaplan-Meier method and the log-rank test;Flow cytometry was used to detect the cell phenotype of CTLA-4,CD80 and CD86derived from the tumor tissue of treated mouse.The expression of IFN-γand TNF-αin the tumor tissue were detected by RT-PCR.The results showed,compared with the two groups which were treated with 5-FU or CIK cells alone,in the 5-FU plus CIK cells combination group,tumor weight was significantly decreased（P〈0.05）,while the expression of CTLA-4in CD45＋cells and CD80/CD86 in CD45-were increased,and the expression of IFN-γ（P〈0.05）and TNF-αin the tumor tissue were also increased.These results suggest that 5-FU plus CIK cells combination therapy is better than the therapies with 5-FU of CIK cells for inhibiting the growth and enhancing cellular immune function in mice with colon cancer.