Pfreundschuh M, Genth B, Kirchner H, Scheurich P, Lindemann A, Steinmetz H T, Schaadt M, Diehl V
Medizinische Klinik, Universität zu Köln.
Onkologie. 1989 Jun;12(3):128-30. doi: 10.1159/000216619.
To find clues as to the possible mechanisms of resistance against the cytotoxic activity of tumor necrosis factor (TNF), we developed TNF-resistant and TNF-sensitive subclones of the human cervic carcinoma cell line ME 180 and the mammary carcinoma cell line BT-20. Resistant subclones were selected by gradually increasing the TNF concentration in the culture medium over 4 months or 20 passages. Resistance to TNF was conserved in the absence of TNF after nearly 3 years and less than 100 passages. There were no differences in the number and affinity of TNF receptors between the sensitive and resistant clones. Similarly, SDS-PAGE of cell lysates showed identical bands. Sensitivity to actinomycin D, mitomycin C, and interferon-gamma was the same. No TNF message could be demonstrated in either subclone. As tumors grown in nude mice derived from the sensitive and resistant clones responded equally well to an intratumoral injection of TNF, we conclude that different mechanisms are responsible for sensitivity and resistance to the cytotoxic effect of TNF in vitro and in vivo.
为了寻找抵抗肿瘤坏死因子（TNF）细胞毒性活性的可能机制线索，我们构建了人子宫颈癌细胞系ME 180和乳腺癌细胞系BT - 20的TNF抗性和TNF敏感亚克隆。通过在4个月或20代培养过程中逐渐提高培养基中TNF的浓度来筛选抗性亚克隆。在没有TNF的情况下，经过近3年且传代次数少于100次后，对TNF的抗性得以保留。敏感克隆和抗性克隆之间TNF受体的数量和亲和力没有差异。同样，细胞裂解物的SDS - PAGE显示出相同的条带。对放线菌素D、丝裂霉素C和γ干扰素的敏感性相同。在任一亚克隆中均未检测到TNF信息。由于源自敏感和抗性克隆的裸鼠体内生长的肿瘤对瘤内注射TNF的反应同样良好，我们得出结论，体外和体内对TNF细胞毒性作用的敏感性和抗性是由不同机制引起的。
