Doyle L A, Hamburger A W, Goldstein L H, Park H J
University of Maryland Cancer Center, Baltimore 21201.
Mol Biother. 1990 Sep;2(3):169-74.
Studies have suggested that recombinant tumor necrosis factor-alpha (TNF-alpha) may potentiate the killing of murine tumor cells by drugs targeted at DNA topoisomerase II. We have examined the combined cytotoxic effects of the topoisomerase-targeted drug etoposide and TNF in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cell lines using clonogenic assays and a novel flow cytometry technique relying on differential uptake of fluorescein diacetate (FDA) and propidium iodide (PI) by viable and nonviable cells. Good correlation of IC50 determinations for etoposide were noted between clonogenic assays and the FDA/PI technique for both classic and variant SCLC cell lines. The effects of etoposide on the classic SCLC line H209 were potentiated by TNF with a decrease in the IC50 from 3.3 microM to 1.0 microM as determined by FDA/PI. Tumor necrosis factor alone had little effect on the growth or cloning efficiency of H209 cells. Tumor necrosis factor alone stimulated the growth and cloning of variant SCLC line N417, but the cytotoxicity of etoposide was not potentiated by TNF in N417 cells. Tumor necrosis factor alone inhibited the growth and cloning of the NSCLC line H125 but exerted a marked protective effect against higher concentrations of etoposide. It appears that the interaction of TNF with etoposide varies between cell lines and between subclasses of human lung cancer.
研究表明，重组肿瘤坏死因子-α（TNF-α）可能增强靶向DNA拓扑异构酶II的药物对小鼠肿瘤细胞的杀伤作用。我们使用克隆形成试验和一种基于活细胞和死细胞对荧光素二乙酸酯（FDA）和碘化丙啶（PI）摄取差异的新型流式细胞术技术，研究了拓扑异构酶靶向药物依托泊苷和TNF在小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC）细胞系中的联合细胞毒性作用。对于经典型和变异型SCLC细胞系，克隆形成试验和FDA/PI技术测定的依托泊苷IC50之间具有良好的相关性。根据FDA/PI测定，TNF增强了依托泊苷对经典SCLC细胞系H209的作用，IC50从3.3微摩尔降至1.0微摩尔。单独的肿瘤坏死因子对H209细胞的生长或克隆效率几乎没有影响。单独的肿瘤坏死因子刺激变异型SCLC细胞系N417的生长和克隆，但在N417细胞中TNF并未增强依托泊苷的细胞毒性。单独的肿瘤坏死因子抑制NSCLC细胞系H125的生长和克隆，但对较高浓度的依托泊苷具有显著的保护作用。看来，TNF与依托泊苷的相互作用在不同细胞系之间以及人类肺癌的不同亚类之间存在差异。
