Tumour blood vessel normalisation by prolyl hydroxylase inhibitor repaired sensitivity to chemotherapy in a tumour mouse model.
Tumour blood vessel normalisation by prolyl hydroxylase inhibitor repaired sensitivity to chemotherapy in a tumour mouse model.
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DOI：
10.1038/srep45621
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发表时间：
2017-03-31
影响因子：
4.6
通讯作者：
Tomita S
中科院分区：
文献类型：
--
作者：
Koyama S;Matsunaga S;Imanishi M;Maekawa Y;Kitano H;Takeuchi H;Tomita S
血管是输送氧气和营养的重要组织结构。在肿瘤组织中，通常会形成异常的血管，这些血管是高渗透和未成熟的，这些组织也有不规则的血管形成和血管内。这种情况会导致肿瘤组织的低灌注量以及低氧和营养耗竭；这也被称为肿瘤微环境，其特征是缺氧、营养耗竭、低pH和高间质压力。这种环境会导致抗癌药物产生耐药性，从而导致抗癌药物剂量的增加，从而导致副作用增加。我们假设，正常化的肿瘤血管将改善肿瘤组织的灌注，重新补充营养，并使肿瘤组织重新充氧。化疗将会更有效，并导致抗癌药物剂量的减少。在这里，我们报告了一种诱导新生血管的药物，它可以改善肿瘤血管异常，如低血流量、血液渗漏和异常血管结构。这些结果不仅可能导致化疗敏感性和组织药物分布的增加，而且还可能上调癌症化疗的效率。这表明肿瘤血管正常化治疗伴随血管生成可能是癌症治疗的一种新策略。
Blood vessels are important tissue structures that deliver oxygen and nutrition. In tumour tissue, abnormal blood vessels, which are hyperpermeable and immature, are often formed; these tissues also have irregular vascularisation and intravasation. This situation leads to hypoperfusion in tumour tissue along with low oxygen and nutrition depletion; this is also called the tumour microenvironment and is characterised by hypoxia, depleted nutrition, low pH and high interstitial pressure. This environment induces resistance to anticancer drugs, which causes an increase in anticancer drug doses, leading to increased side effects. We hypothesised that normalised tumour blood vessels would improve tumour tissue perfusion, resupply nutrition and re-oxygenate the tumour tissue. Chemotherapy would then be more effective and cause a decrease in anticancer drug doses. Here we report a neovascularisation-inducing drug that improved tumour vascular abnormalities, such as low blood flow, blood leakage and abnormal vessel structure. These results could lead to not only an increased chemo-sensitivity and tissue-drug distribution but also an up-regulated efficiency for cancer chemotherapy. This suggests that tumour blood vessel normalisation therapy accompanied by angiogenesis may be a novel strategy for cancer therapy.