Valle P, Timeus F, Piglione M, Rosso P, di Montezemolo L C, Crescenzio N, Marranca D, Ramenghi U
Pediatric Department, University of Torino, Italy.
Pediatr Hematol Oncol. 1995 Sep-Oct;12(5):439-46. doi: 10.3109/08880019509009473.
Desferrioxamine (DFO) has shown anti-proliferative and cytotoxic effects on several tumor cells. DFO is used at present in the treatment of neuroblastoma in combination with chemotherapy (D-CECaT regimen: cyclophosphamide, etoposide, carboplatin, and thiotepa). We compared the effect of continuous or intermittent exposures to DFO on 3H-thymidine uptake, viability, and cell cycle of human neuroblastoma (NB) cell lines. Our results show that continuous exposures to DFO cause dose- and time-dependent cytotoxicity of NB cells, while intermittent exposures result in significant NB cell toxicity only when using high DFO concentrations. By 3H-thymidine uptake, a significant inhibition of proliferation was observed only in continuous exposures. In addition, a consistent arrest in G1 phase was detected only in cultures treated continuously with high DFO concentrations. Our data indicate that 3H-thymidine uptake, viability, and cell cycle changes are proportional to the extent of exposure and concentration of DFO, suggesting that in vivo DFO continuous infusion may improve anti-neuroblastoma activity.
去铁胺(DFO)已显示出对多种肿瘤细胞的抗增殖和细胞毒性作用。目前,DFO与化疗联合用于治疗神经母细胞瘤(D-CECaT方案:环磷酰胺、依托泊苷、卡铂和噻替派)。我们比较了持续或间歇暴露于DFO对人神经母细胞瘤(NB)细胞系的3H-胸腺嘧啶核苷摄取、活力和细胞周期的影响。我们的结果表明,持续暴露于DFO会导致NB细胞产生剂量和时间依赖性细胞毒性,而间歇暴露仅在使用高DFO浓度时才会导致显著的NB细胞毒性。通过3H-胸腺嘧啶核苷摄取,仅在持续暴露中观察到增殖的显著抑制。此外,仅在连续用高DFO浓度处理的培养物中检测到G1期的持续停滞。我们的数据表明,3H-胸腺嘧啶核苷摄取、活力和细胞周期变化与DFO的暴露程度和浓度成正比,这表明体内DFO持续输注可能会提高抗神经母细胞瘤活性。