Combined actions of 5-fluorouracil and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea on human colonic carcinoma cells in vitro.

Two lines of human colonic carcinoma cells have different sensitivities to 5-fluorouracil and 1-(2-chlorethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU). The growth of the BE line is 50% inhibited by 330 microM 5-fluorouracil and 15 microM methyl-CCNU, and the HT-29 line is 50% inhibited by 85 and 140 microM, respectively. On cloning, 50% of BE cells are killed by 500 microM 5-fluorouracil and 6 microM methyl-CCNU, and the HT-29 cells are killed by 250 and 120 microM respectively. When the drugs were combined, there were additive effects which occurred in cell growth of both lines and killing of BE cells. Synergism occurred in killing HT-29 cells when a low concentration of 5-fluorouracil was combined with methyl-CCNU. The synergism did not increase with increasing concentrations of 5-fluorouracil. Both drugs caused growth delay of spheroids (HT-29 cells), an effect that was additive when the drugs were combined. Growth inhibition of both lines in monolayer culture by 5-fluorouracil was more sensitive than was cell killing or inhibition of spheroid growth but, with methyl-CCNU, killing of BE cells was more sensitive than was growth inhibition. HT-29 cells showed similar sensitivity to methyl-CCNU in all three systems. The type and sensitivity of drug effect seen in vitro depends on the particular drug used, the cell line tested, and the parameter measured.