Tumor-selective blood flow decrease induced by an angiotensin converting enzyme inhibitor, temocapril hydrochloride
Tumor-selective blood flow decrease induced by an angiotensin converting enzyme inhibitor, temocapril hydrochloride
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DOI：
10.1111/j.1349-7006.2000.tb00940.x
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发表时间：
2000-02-01
期刊：
影响因子：
--
通讯作者：
Sato, Y
中科院分区：
文献类型：
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作者：
Hori, K;Saito, S;Sato, Y
为了提高对癌症的化疗效果，必须优先将抗癌药物输送到癌细胞，并将药物长期保留在癌细胞中。体内抗癌药物暴露时间的延长可以通过减少抗癌药物给药后的肿瘤组织血流量来实现。本研究表明，血管紧张素转换酶抑制剂盐酸替莫普利能显著降低大鼠吉田肉瘤亚系LY80肿瘤的总血流量，而对肝、肾、骨髓和脑的血流无明显影响。在血流量大于20ml/min/100g的肿瘤区域，替莫普利使TBF下降约50%，在TBF约为20ml/min/100g的肿瘤区域，加入替莫普利后，TBF降至3ml/min/100g以下，且在实验2 h内未见恢复。这些发现不仅在大肿瘤中获得，而且在透明腔内生长的微灶中也得到了发现。此外，即使在血管紧张素II增加肿瘤总血流量的情况下给予替莫普利，肿瘤总血流量也立即下降。使用这项技术，应该可以在更长的时间内选择性地将抗癌药物捕获到肿瘤组织中。
To enhance chemotherapeutic efficacy against cancer, it is important to deliver anticancer drugs preferentially to cancer cells and to retain the drugs there for a prolonged time. The in vivo prolongation of the exposure time of anticancer drugs in tumors can be accomplished by decreasing tumor tissue blood flow (tBF) after anticancer drug administration. The present study demonstrated that temocapril hydrochloride, an angiotensin converting enzyme inhibitor, decreases tumor tBF markedly in LY80 tumor, a subline of Yoshida sarcoma in the rat, without affecting the blood flow in Liver, kidney, bone marrow, and brain. In tumor areas with flow of above 20 ml/min/ 100 g, the tBF decreased by approximately 50% due to temocapril, In tumor areas with tBF of about 20 ml/min/100 g, it became less than 3 ml/min/100 g with temocapril and did not recover during the 2 h experiment. These findings were obtained not only in large tumors, but also in microfoci growing within a transparent chamber. Furthermore, even when temocapril was administered under the condition of increased tumor tBF by administering angiotensin II, tumor tBF decreased immediately. Using this technique, it should be possible to trap anticancer drugs selectively in tumor tissue for an extended period of time.