阿霉素与Fas抗体对提高肺癌细胞凋亡的实验研究

目的 研究阿霉素(ADM)与Fas抗体在肺癌细胞的细胞毒作用中是否具有协同作用。方法 MTT法检测细胞毒作用，荧光染色法测定癌细胞凋亡效应。结果 NCL446人类肺癌细胞株及12例手术新鲜肺癌标本与ADM及Fas抗体共同培养显示有显的细胞毒协同效应。Fas抗体与ADM亦有协同的诱导凋亡效应。Fas抗体可以提高NCL446细胞内ADM的聚集量。ADM可以增强NCL446细胞表面的Fas表达。结论 实验结果表明，Fas抗体与ADM共培养可以克服肺癌细胞的耐药性。协同效应不仅在肺癌细胞株中发现，而且存在于手术切除的肺癌标本中。说明ADM与Fas相关免疫制剂联合有潜在的临床应用前景。

An Experimental study of Using Anticancer chemotherapeutic Drugs and Fas Antigen Togetaer in cytotoxioty against lung cancer cells

Purpose The resistance of blader cancer to anticancer chemotherapeutic drugs is a major problem. Several immunotherapeutic approaches have been developed to treat drug resistant tumor cells. The Fas antigen(Fas) Fas ligand pathway is involved in cytotoxic T lymphocyte and nayural killer cell mediated cytotoxicity. Like the Fas ligand, anti Fas monoclonal antibody(mAb) induces apoptosis in tumor cells expressing Fas. Several anticancer drugs also mediate apoptosis and may share with Fas common intracellular pathways leading to cell killing. This study was to investgat the Effects of anticancer drugs synergizes with anti Fas mAb in cytotoxicity against lung cancer cells.Materials The cytotoxicity was determined by 1 day microculture tetrazolium dye assay. Synergy was assessed by isobolographic analysis.Results The treatment of NCL446 lung tumor cell ling and twelve freshly derived hunan lung cancer cells with a combination of anti Fas mAb and doxorubicin resulted in a synergisyic cytotoxic effect. The synergy achieved in cytotoxicity with anti Fas mAb and doxorubicin was also achieved in apoptosis. Incubation of NCL446 cells with anti Fas nAb increased the intracellular accumulation of doxorubicin. The treatment with doxorubicin enhanced the expression of Fas on NCL446 cells. Conclusions This study demonstrates thata combination treatment of lung cancer cells with anti Fas mAb and doxorubicin overcomes their resistance. Synergy was achieved with established lung cancer cells and freshly isolated lung cancer cells. In addition, the sensitization requirs low concentrations of doxorubicin, supporting the potential in vivo application of combination of doxorubicin and immunotherapy in the treatment of doxorubicin and/or immunotherapy resistant lung cancer.