Zirvi K A, van der Bosch J, Kaplan N O
Cancer Res. 1982 Sep;42(9):3793-7.
In vitro responses of 4 xenografted human colon tumors (T183, T219, T245, and T348) to various doses of 4'-deoxydoxorubicin have been investigated. The individual tumors showed marked differences in drug responsiveness, ranging from high sensitivity at low doses (T219; 125 ng/ml) to very low sensitivity at high doses (T245; 4000 ng/ml). The sensitivity ranking deduced from these in vitro experiments correlates well with the ranking deduced earlie (Guiliani et al., Int. J. Cancer, 27: 5-13, 1981) from in vivo drug treatments of transplants of these tumors in the nude mouse. The effect of in vitro drug treatment (4'-deoxydoxorubicin; 250 ng/ml; 1-hr incubation) on the in vivo growth of one of the tumors, T219, in nude mice was investigated. Growth of the tumor in nude mice was markedly delayed by pretreatments in vitro with 4'-deoxydoxorubicin. Furthermore, in vitro responsiveness of the T219 tumor was investigated following in vivo and in vitro treatment of the tumor with 4'-deoxydoxorubicin. Both of the pretreatments produced very similar decreases in drug responsiveness to all of the doxorubicin derivatives tested (4'-deoxydoxorubicin, 4'-O-methyldoxorubicin, 4'-epidoxorubicin, 4-demethoxydoxorubicin, and N-trifluoroacetyldoxorubicin-14-valeriate).
研究了4种异种移植的人结肠肿瘤(T183、T219、T245和T348)对不同剂量4'-脱氧阿霉素的体外反应。各个肿瘤在药物反应性上表现出显著差异,从低剂量时的高敏感性(T219;125纳克/毫升)到高剂量时的非常低敏感性(T245;4000纳克/毫升)。从这些体外实验得出的敏感性排名与早期(Guiliani等人,《国际癌症杂志》,27:5 - 13,1981)对这些肿瘤在裸鼠体内移植进行药物治疗得出的排名密切相关。研究了体外药物处理(4'-脱氧阿霉素;250纳克/毫升;孵育1小时)对其中一种肿瘤T219在裸鼠体内生长的影响。用4'-脱氧阿霉素进行体外预处理显著延迟了裸鼠体内肿瘤的生长。此外,在用4'-脱氧阿霉素对T219肿瘤进行体内和体外处理后,研究了其体外反应性。两种预处理对所有测试的阿霉素衍生物(4'-脱氧阿霉素、4'-O-甲基阿霉素、4'-表阿霉素、4-去甲氧基阿霉素和N-三氟乙酰阿霉素-14-戊酸酯)的药物反应性降低非常相似。