Lethal efficacy of doxorubicin on human medullary thyroid carcinoma cells in vitro

Cytotoxicity of doxorubicin was evaluated on a cultured human thyroid carcinoma (MTC) cell line, TT, by the colony-formation technique. The concentration-dependent survival curve showed a biphasic exponential pattern. Doxorubicin in concentrations of 5 X 10(-9) to 3 X 10 (-5) M produced a 15% to 71% cell kill after 1 hr of treatment. Mean lethal concentrations, 0.6 and 59 micrograms/ml, were considerably higher than those reported for cells of other tumors. Prolonged continuous treatment with a single concentration (1 X 10(-8) M) resulted in a cell kill of only 39% by 20 hr, and no further improvement was achieved with extended treatment of up to 48 hr. That doxorubicin activity was not enhanced by prolonged treatment was shown by controls not to be due to inactivation of the drug. Our results suggest that TT cells are somewhat resistant to doxorubicin and that acute administration of larger doses rather than continuous infusion of small doses should perhaps be considered when doxorubicin is used in patients with metastatic MTC.