Yang K P, Samaan N A
Department of Medical Specialties, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030.
Anticancer Res. 1988 Mar-Apr;8(2):245-8.
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.
采用集落形成技术,在人甲状腺癌细胞系TT上评估了阿霉素的细胞毒性。浓度依赖性存活曲线呈双相指数模式。浓度为5×10⁻⁹至3×10⁻⁵ M的阿霉素在处理1小时后可导致15%至71%的细胞死亡。平均致死浓度分别为0.6和59微克/毫升,显著高于其他肿瘤细胞的报道值。用单一浓度(1×10⁻⁸ M)进行长时间连续处理,到20小时时细胞死亡率仅为39%,延长至48小时的处理也未进一步提高细胞死亡率。对照显示,长时间处理并未增强阿霉素活性,这并非由于药物失活所致。我们的结果表明,TT细胞对阿霉素有一定抗性,因此当阿霉素用于转移性甲状腺髓样癌患者时,或许应考虑给予大剂量冲击给药而非小剂量持续输注。