Bartholeyns J
Eur J Cancer Clin Oncol. 1983 Apr;19(4):567-72. doi: 10.1016/0277-5379(83)90123-2.
The effects of DL-alpha-difluoromethylornithine (DFMO), a specific, irreversible inhibitor of ornithine decarboxylase (ODC), on tumors induced in the muscle of C57BL mice by Lewis lung (LL) carcinoma cells and on the development of lung metastases have been investigated. ODC activity and putrescine, spermidine and spermine concentrations were increased both during the early phase of development of the primary LL tumor and in the lung coinciding with the development of metastases. Oral treatment with DFMO (2% aqueous solution as sole drinking fluid, equivalent to 4 g DFMO/kg/day) decreased markedly the ODC activity and the putrescine and spermidine concentrations of the primary tumor, and stimulated S-adenosyl-L-methionine decarboxylase activity. ODC activity and putrescine and spermidine concentrations were similarly markedly reduced in the metastatic lung by DFMO treatment. By comparison with untreated controls, DFMO treatment from day 1 after inoculation resulted in an 81% decrease in tumor size and a 92% reduction of lung metastases by day 20 and prolonged the mean survival time from 20.2 to 28.8 days. The same treatment regimen started 8 days after tumor inoculation resulted in a 52% inhibition of tumor growth and an 82% reduction of lung metastases, and prolonged the mean survival time to 24.9 days. The clear antitumoral effects obtained with DFMO on this animal metastatic cancer indicate its potential value in the treatment of metastases in humans.
已研究了鸟氨酸脱羧酶（ODC）的特异性不可逆抑制剂DL-α-二氟甲基鸟氨酸（DFMO）对Lewis肺癌（LL）细胞在C57BL小鼠肌肉中诱导的肿瘤以及肺转移发生发展的影响。在原发性LL肿瘤发展的早期阶段以及与转移发生发展同时的肺中，ODC活性以及腐胺、亚精胺和精胺浓度均升高。用DFMO口服治疗（2%水溶液作为唯一饮用水，相当于4 g DFMO/kg/天）可显著降低原发性肿瘤的ODC活性以及腐胺和亚精胺浓度，并刺激S-腺苷-L-甲硫氨酸脱羧酶活性。通过DFMO治疗，转移性肺中的ODC活性以及腐胺和亚精胺浓度也同样显著降低。与未治疗的对照组相比，接种后第1天开始用DFMO治疗，到第20天时肿瘤大小减少81%，肺转移减少92%，平均生存时间从20.2天延长至28.8天。在肿瘤接种后8天开始相同的治疗方案，可使肿瘤生长抑制52%，肺转移减少82%，并将平均生存时间延长至24.9天。DFMO对这种动物转移性癌症所产生的明显抗肿瘤作用表明其在治疗人类转移瘤方面具有潜在价值。
