Quemener V, Moulinoux J P, Havouis R, Seiler N
Laboratoire de Biologie Cellulaire, Centre Hospitalier Universitaire de Rennes, France.
Anticancer Res. 1992 Sep-Oct;12(5):1447-53.
We reported previously that polyamine deprivation by feeding a polyamine deficient diet combined with gastrointestinal tract decontamination and polyamine oxidase inhibition considerably enhanced the antitumoral effect of DFMO, a selective inhibitor of ornithine decarboxylase. The combination of polyamine deprivation and administration of well established cytotoxic drugs was expected to improve further the antitumoral effect of polyamine deprivation in Lewis lung carcinoma grafted in mice. Simultaneous treatment, i.e. administration of the cytotoxic drugs during the polyamine deprivation regimen, reduced tumor growth, but enhanced toxic effects. By alternating treatment and polyamine deprivation (1st day methotrexate (1.7 mg/kg), 2nd day cyclophosphamide (90 mg/kg), 3rd day vindesine (0.25 mg/kg), followed by five days of polyamine deprivation), tumor growth was reduced by 90% and an increase of 64% in the survival time of the animals was observed, demonstrating that a significant enhancement of the efficacy of chemotherapy was achieved without concomitant enhancement of toxic effects.
我们之前报道过，通过喂食缺乏多胺的饮食并结合胃肠道去污和多胺氧化酶抑制来剥夺多胺，可显著增强鸟氨酸脱羧酶的选择性抑制剂DFMO的抗肿瘤作用。多胺剥夺与已确立的细胞毒性药物联合使用，有望进一步提高在移植到小鼠体内的Lewis肺癌中多胺剥夺的抗肿瘤效果。同时治疗，即在多胺剥夺方案期间给予细胞毒性药物，可减少肿瘤生长，但会增强毒性作用。通过交替进行治疗和多胺剥夺（第1天给予甲氨蝶呤（1.7 mg/kg），第2天给予环磷酰胺（90 mg/kg），第3天给予长春地辛（0.25 mg/kg），随后进行五天的多胺剥夺），肿瘤生长减少了90%，并且观察到动物的存活时间增加了64%，这表明在不伴随毒性作用增强的情况下，化疗疗效得到了显著提高。
