Development of tumour cell resistance to tumour necrosis factor does not confer resistance to cytotoxic drugs.

Tumour necrosis factor (TNF) is a protein product of macrophages with potential anti-cancer activity. As with other anti-cancer agents, tumour cells can develop resistance to the cytotoxic effects of TNF. The aim of his study was to see whether development of resistance to TNF resulted in a concomitant resistance to other anti-cancer agents, in particular those associated with multidrug resistance. Three TNF-susceptible tumour cell lines (L929, U937 and RK13) and their TNF-resistant sublines were compared for susceptibility in vitro to several cytotoxic drugs. The TNF-resistant sublines were not significantly more resistant to these drugs. In addition, an L929 subline selected for resistance to actinomycin D retained its susceptibility to TNF. These observations show that tumour cell resistance to TNF develops independently of resistance to cytotoxic drugs.