Dubois M F, Ferrieux C, Lebon P
INSERM U 43, Hôpital Saint-Vincent de Paul, Paris, France.
Cancer Res. 1989 Oct 15;49(20):5618-22.
A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (TNF-alpha), interferons (IFN-alpha, IFN-beta, and IFN-gamma) and heat-stress was demonstrated in vitro. The toxicity of these agents was assessed in the human cervical carcinoma HeLa cell line: the toxic effect was greatly increased when cells pretreated with IFNs or TNF were submitted to a 1-h heat-shock at 45 degrees C. Moreover if the heat-stress followed simultaneous treatment with both cytokines, a synergistic effect between these treatments could be observed. The same observations were made for two other transformed cell lines: the oral epidermoid carcinoma KB cells and the hepatocarcinoma PLC/PRF/5 cells. In contrast, the survival of normal cells (normal foetal lung MRC5 cells and foreskin F 7000 fibroblasts) was only slightly decreased by such treatments. These results suggest that combining a heat-stress with cytokines treatment might be one way of enhancing the sensitivity of cancer cells to the growth inhibitory effects of the individual cytokines.
体外实验证明，重组人肿瘤坏死因子（TNF-α）、干扰素（IFN-α、IFN-β和IFN-γ）与热应激联合使用时，细胞毒性作用呈协同增强。在人宫颈癌HeLa细胞系中评估了这些药物的毒性：当用干扰素或肿瘤坏死因子预处理的细胞在45℃下进行1小时热休克时，毒性作用显著增强。此外，如果在两种细胞因子同时处理后再进行热应激处理，则可观察到这些处理之间的协同作用。对另外两种转化细胞系也得到了相同的结果：口腔表皮样癌KB细胞和肝癌PLC/PRF/5细胞。相比之下，这些处理对正常细胞（正常胎儿肺MRC5细胞和包皮F 7000成纤维细胞）的存活率仅有轻微影响。这些结果表明，热应激与细胞因子治疗相结合可能是增强癌细胞对单一细胞因子生长抑制作用敏感性的一种方法。
