Chitnis M P, Viladkar A B, Juvekar A S
Cellular Chemotherapy Unit, Tata Memorial Center, Parel, Bombay, India.
Neoplasma. 1990;37(6):619-26.
Pentoxifylline (PTX) is a methylxanthine used clinically in the treatment of intermittent claudication. It is an active hemorheological agent used for the treatment of defective microcirculation. The use of the anticancer agent vincristine is limited by its toxicity to normal body tissues. The data presented in the present paper show that it is possible to achieve greater cell-kill by using vincristine in combination with pentoxifylline. The effect of pentoxifylline alone and in combination with vincristine was studied using membrane filtration technique in P388 leukemia (P388) and its subline P388/DOX resistant to doxorubicin and cross-resistant to vincristine. Pentoxifylline (100 mumol/l) had minimal inhibitory effect on DNA biosynthesis in P388 leukemia cells. Vincristine, at the concentration employed in this study did not show significant inhibition of DNA biosynthesis confirming multidrug resistant nature of P388/DOX cells. Pentoxifylline had a dose-sparing effect, wherein it enhanced the antiproliferative activity of vincristine at a clinically achievable concentration. The studies on reversibility of inhibition of DNA biosynthesis in P388/DOX cells pretreated with vincristine and pentoxifylline showed the irreversible nature of the effect of combination of vincristine and pentoxifylline. This observation warrants the possible use of pentoxifylline as an adjuvant in cancer chemotherapy.
己酮可可碱（PTX）是一种甲基黄嘌呤，临床上用于治疗间歇性跛行。它是一种活性血液流变学药物，用于治疗微循环缺陷。抗癌药物长春新碱的使用受到其对正常身体组织毒性的限制。本文给出的数据表明，将长春新碱与己酮可可碱联合使用有可能实现更大的细胞杀伤效果。采用膜过滤技术，在P388白血病（P388）及其对阿霉素耐药且对长春新碱交叉耐药的亚系P388/DOX中研究了己酮可可碱单独使用及与长春新碱联合使用的效果。己酮可可碱（100 μmol/l）对P388白血病细胞的DNA生物合成具有最小抑制作用。在本研究中使用的浓度下，长春新碱未显示出对DNA生物合成的显著抑制，证实了P388/DOX细胞的多药耐药性质。己酮可可碱具有剂量节省效应，即在临床可达到的浓度下增强了长春新碱的抗增殖活性。对用长春新碱和己酮可可碱预处理的P388/DOX细胞中DNA生物合成抑制的可逆性研究表明，长春新碱和己酮可可碱联合作用的效果具有不可逆性。这一观察结果表明己酮可可碱有可能作为癌症化疗的佐剂。
