A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs.
A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs.
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DOI：
10.1038/sj.bjc.6600296
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发表时间：
2002-05-20
影响因子：
8.8
通讯作者：
Kubota, K
中科院分区：
文献类型：
--
作者：
Hori, K;Saito, S;Kubota, K
在以前的研究中，我们使用皮下LY 80肿瘤（吉田肉瘤的一个亚系），佐藤肺癌，和甲基胆蒽诱导的原发性肿瘤，证明了一种新的水溶性考布他汀A-4衍生物，AC 7700，突然和不可逆地停止肿瘤血流。由于这种营养供应中断，在肿瘤内诱导了广泛的坏死。在本研究中，我们研究了AC 7700是否以相同的方式对生长在肝脏、胃、肾脏、肌肉和淋巴结中的实体瘤起作用。用氢清除法测定肿瘤血流量和AC 7700引起的肿瘤血流量变化。在针对转移的癌症化疗模型中，将LY 80细胞（2×106）注射到侧尾静脉中，并且从肿瘤细胞注射后第7天开始，以10 mg kg−1的AC 7700以2天的间隔静脉注射5次。将肿瘤的数量和大小与对照组进行比较。采用大鼠透明小室内种植的Sato肺癌模型，直接观察肿瘤血流的变化及AC 7700对微小肿瘤的治疗作用。AC 7700导致在各种组织和器官中发展的所有LY 80肿瘤的肿瘤血流量显著减少，并且所有肿瘤的生长（包括淋巴结转移和微肿瘤）受到抑制。在每个肿瘤中，肿瘤血流量在AC 7700给药后立即开始下降，并在注射后约30分钟达到最低值。在许多肿瘤毛细血管中，AC 7700给药后3分钟内血流完全停止。这些结果表明，AC 7700对生长在各种组织和器官中的肿瘤以及转移有效。我们得出结论，AC 7700诱导的肿瘤血流止血可能成为所有癌症的有效治疗策略，包括难治性癌症，因为治疗效果与肿瘤部位和特定类型的癌症无关。英国癌症杂志（2002）86，1604-1614。DOI：10.1038/sj/bjc/6600296 www.bjcancer.com © 2002英国癌症研究中心
In a previous study, we used subcutaneous LY80 tumours (a subline of Yoshida sarcoma), Sato lung carcinoma, and methylcholanthrene-induced primary tumours, to demonstrate that a novel water-soluble combretastatin A-4 derivative, AC7700, abruptly and irreversibly stopped tumour blood flow. As a result of this interrupted supply of nutrients, extensive necrosis was induced within the tumour. In the present study, we investigated whether AC7700 acts in the same way against solid tumours growing in the liver, stomach, kidney, muscle, and lymph nodes. Tumour blood flow and the change in tumour blood flow induced by AC7700 were measured by the hydrogen clearance method. In a model of cancer chemotherapy against metastases, LY80 cells (2×106) were injected into the lateral tail vein, and AC7700 at 10 mg kg−1 was injected i.v. five times at intervals of 2 days, starting on day 7 after tumour cell injection. The number and size of tumours were compared with those in the control group. The change in tumour blood flow and the therapeutic effect of AC7700 on microtumours were observed directly by using Sato lung carcinoma implanted in a rat transparent chamber. AC7700 caused a marked decrease in the tumour blood flow of all LY80 tumours developing in various tissues and organs and growth of all tumours including lymph node metastases and microtumours was inhibited. In every tumour, tumour blood flow began to decrease immediately after AC7700 administration and reached a minimum at approximately 30 min after injection. In many tumour capillaries, blood flow completely stopped within 3 min after AC7700 administration. These results demonstrate that AC7700 is effective for tumours growing in various tissues and organs and for metastases. We conclude that tumour blood flow stanching induced by AC7700 may become an effective therapeutic strategy for all cancers, including refractory cancers because the therapeutic effect is independent of tumour site and specific type of cancer. British Journal of Cancer (2002) 86, 1604–1614. DOI: 10.1038/sj/bjc/6600296 www.bjcancer.com © 2002 Cancer Research UK