INHIBITION OF GROWTH OF COLON-38 ADENOCARCINOMA BY VINBLASTINE AND COLCHICINE - EVIDENCE FOR A VASCULAR MECHANISM
INHIBITION OF GROWTH OF COLON-38 ADENOCARCINOMA BY VINBLASTINE AND COLCHICINE - EVIDENCE FOR A VASCULAR MECHANISM
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DOI：
10.1016/0277-5379(91)90391-p
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发表时间：
1991-01-01
影响因子：
8.4
通讯作者：
ZWI, LJ
中科院分区：
文献类型：
--
作者：
BAGULEY, BC;HOLDAWAY, KM;ZWI, LJ
长春碱或秋水仙碱，腹膜内给予晚期皮下结肠38肿瘤的B6 D2 F1小鼠，诱导实质性肿瘤生长延迟，在治疗8小时内开始进行性发展出血性坏死。 两个多药耐药P388白血病亚系，难治长春碱和长春新碱时，生长为腹膜内腹水，是敏感的坏死诱导时，生长为皮下肿瘤。 两种荧光标记物的血管标记表明，长春新碱在治疗后4小时内显著降低了肿瘤血流量。 长春碱、长春新碱和秋水仙碱的作用与肿瘤坏死因子α的作用相似，因为：（a）诱导了相似的肿瘤坏死和血流变化，（B）同时给予5-羟色胺拮抗剂环庚替丁可预防肿瘤坏死，（c）血浆硝酸盐水平升高，表明L-精氨酸氧化为一氧化氮的刺激。 结果表明，长春花生物碱和秋水仙碱作用于实体瘤宿主细胞介导的血管效应，以及直接微管蛋白介导的细胞毒性。
Vinblastine or colchicine, administered intraperitoneally to B6D2F1 mice with advanced subcutaneous colon 38 tumours, induced substantial tumour growth delays with progressive development of haemorrhagic necrosis beginning within 8 hours of treatment. Two multidrug-resistant P388 leukaemia sublines, refractory to vinblastine and vincristine when grown as intraperitoneal ascites, were sensitive to necrosis induction when grown as subcutaneous tumours. Vascular labelling with two fluorescent markers indicated that vincristine substantially reduced tumour blood flow within 4 hours after treatment. The effects of vinblastine, vincristine and colchicine were similar to those of tumour necrosis factor alpha in that: (a) similar tumour necrosis and blood flow changes were induced, (b) coadministration of the serotonin antagonist cyproheptidine prevented tumour necrosis and (c) plasma nitrate levels were elevated, indicative of the stimulation of oxidation of L-arginine to nitric oxide. The results suggest that vinca alkaloids and colchicine act on solid tumours by host cell-mediated vascular effects as well as by direct tubulin-mediated cytotoxicity.