Theiss J C, Stoner G D, Shimkin M B
Cancer Res. 1977 Jan;37(1):305-9.
An in vitro-in vivo system for screening potentially effective drugs against solid tumors is described. Drug toxicity to plateau-phase pulmonary adenoma cells is used as an in vitro screen for potential activity against solid tumors, since both plateau phase cultured cell populations and solid tumors are composed predominantly of nondividing cells. The effect of drugs with in vitro activity on the rate of appearance of urethan-induced adenomas on the lung surface of strain A mice in vivo is used to assess drug efficacy in the treatment of solid tumors, taking into consideration drug toxicity to and drug metabolism by the host. Arabinosylcytosine and hydroxyurea were ineffective against plateau phase cells in vitro, even at high concentrations (5 to 10 mg/ml), and did not affect pulmonary adenoma growth in vivo, even at toxic doses (arabinosylcytosine, 80 mg/kg; hydroxyurea, 800 mg/kg), as would be expected with these cell cycle-active drugs. Adriamycin, an effective agent against human solid tumors, was cytotoxic to plateau phase cultured cells (0% survivors at 1 mug/ml), and a dose of 2 mg/kg completely inhibited pulmonary adenoma growth in mice. Thus, this pulmonary adenoma bioassay would appear to effectively select for drugs which may be active against solid tumors in humans.
本文描述了一种用于筛选针对实体瘤潜在有效药物的体外-体内系统。由于平台期培养的细胞群体和实体瘤主要都由非分裂细胞组成，因此将药物对平台期肺腺癌细胞的毒性用作针对实体瘤潜在活性的体外筛选指标。考虑到药物对宿主的毒性和药物代谢情况，利用具有体外活性的药物对A系小鼠肺表面由乌拉坦诱导的腺瘤出现速率的影响，来评估药物在实体瘤治疗中的疗效。阿糖胞苷和羟基脲即使在高浓度（5至10毫克/毫升）下对体外平台期细胞也无效，并且即使在有毒剂量（阿糖胞苷，80毫克/千克；羟基脲，800毫克/千克）下，也不影响体内肺腺瘤的生长，这与这些细胞周期活性药物的预期情况一致。阿霉素是一种对人类实体瘤有效的药物，对平台期培养细胞具有细胞毒性（1微克/毫升时存活率为0%），2毫克/千克的剂量可完全抑制小鼠肺腺瘤的生长。因此，这种肺腺瘤生物测定法似乎能有效地筛选出可能对人类实体瘤有活性的药物。
