Gerharz C D, Ramp U, Reinecke P, Ressler U, Dienst M, Marx N, Friebe U, Engers R, Pollow K, Gabbert H E
Institute of Pathology, Heinrich Heine-University, Düsseldorf, Germany.
Anticancer Res. 1996 Jul-Aug;16(4A):1633-41.
Since no effective therapeutic approach is known so far for metastatic renal cell carcinoma (RCC), we analyzed the anti-proliferative effects of TNF-alpha and retinoic acid (RA), applied either alone or in combination on 7 different RCC cell lines in vitro. In 5 out of 7 cell lines, a significant (p < 0.05) dose-dependent inhibition of tumor cell proliferation became evident after exposure to TNF-alpha, the response being of modest magnitude in 5 cell lines. In 2 cell lines the effects were more pronounced with a reduction of cell viability to 55 +/- 11% of the control. Northern blot analysis revealed no expression of TNF-alpha and p75 TNF-receptor in any cell line. All the cell lines showed p55 TNF-receptor mRNA. Scatchard analysis revealed no correlation between TNF-alpha receptor status and growth inhibitory response to TNF-alpha, the number of TNF-receptors per cell ranging from 0 to 3,976, and the affinity values from Kd = 0.621 nmol/l to Kd = 4.28 nmol/l. Exposure to RA alone resulted in significant (p < 0.05), but modest growth inhibition in 2 out of 7 cell lines with a reduction of cell viability to 83 +/- 1% of the control. In 2 out of 7 cell lines, combination of RA and TNF-alpha was significantly (p < 0.05) more effective than the single application of each compound. Northern blot analysis revealed no transcripts of CRABP I and retinoic acid receptor (RAR)-beta. All the cell lines expressed RAR-alpha mRNA and one cell line additionally expressed RAR-gamma mRNA. A correlation between RAR status and RA response was not seen.
由于目前尚无已知的针对转移性肾细胞癌（RCC）的有效治疗方法，我们分析了单独或联合应用肿瘤坏死因子-α（TNF-α）和视黄酸（RA）对7种不同RCC细胞系的体外抗增殖作用。在7种细胞系中的5种中，暴露于TNF-α后，肿瘤细胞增殖出现显著（p<0.05）的剂量依赖性抑制，在5种细胞系中反应程度适中。在2种细胞系中，细胞活力降低至对照的55±11%，效果更为明显。Northern印迹分析显示，任何细胞系中均未检测到TNF-α和p75 TNF受体的表达。所有细胞系均显示有p55 TNF受体mRNA。Scatchard分析显示，TNF-α受体状态与对TNF-α的生长抑制反应之间无相关性，每个细胞的TNF受体数量为0至3976，亲和值为Kd = 0.621 nmol/l至Kd = 4.28 nmol/l。单独暴露于RA导致7种细胞系中的2种出现显著（p<0.05）但适度的生长抑制，细胞活力降低至对照的83±1%。在7种细胞系中的2种中，RA与TNF-α联合使用比单独应用每种化合物显著（p<0.05）更有效。Northern印迹分析未检测到细胞视黄酸结合蛋白I（CRABP I）和视黄酸受体（RAR）-β的转录本。所有细胞系均表达RAR-α mRNA，一种细胞系还表达RAR-γ mRNA。未发现RAR状态与RA反应之间存在相关性。
