Anti-angiogenic and anti-inflammatory effects of statins: relevance to anti-cancer therapy.
Anti-angiogenic and anti-inflammatory effects of statins: relevance to anti-cancer therapy.
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DOI：
10.2174/156800905774932824
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发表时间：
2005-12
影响因子：
3
通讯作者：
Józkowicz A
中科院分区：
文献类型：
--
作者：
Dulak J;Józkowicz A
血管生成是实体瘤生长所必需的，血管生成因子也参与血液恶性肿瘤的进展。因此，靶向血管的形成被认为是癌症治疗中有前途的策略。有趣的是，除了证明新的抗血管生成化合物的一些有益作用之外，关于已经可用的药物的活性的最近数据指出它们在抗血管生成治疗中的潜在应用。其中包括他汀类药物，3-羟基-3-甲基戊二酰辅酶A还原酶的抑制剂。他汀类药物在治疗心血管疾病中的高胆固醇血症方面非常有效;然而，它们的作用是多效性的，有些与胆固醇合成的抑制不直接相关。一些报告特别强调了他汀类药物的促血管生成作用，这是由低纳摩尔浓度引起的，被认为对心血管疾病的治疗有益。另一方面，在微摩尔浓度下观察到的他汀类药物的抗血管生成活性可能对癌症治疗具有特殊意义。这些作用是通过抑制内皮细胞的增殖和迁移以及诱导内皮细胞凋亡引起的。此外，他汀类药物介导的抑制血管内皮生长因子的合成，主要的血管生成介质，可能有助于衰减血管生成。有研究表明，他汀类药物的抗癌作用可用于癌症治疗。然而，几项旨在通过高剂量他汀类药物治疗抑制肿瘤生长的临床试验并未提供结论性数据。在此，这些结果的原因进行了讨论，并提出了进一步研究的理由。
Angiogenesis is indispensable for the growth of solid tumors and angiogenic factors are also involved in the progression of hematological malignancies. Targeting the formation of blood vessels is therefore regarded as a promising strategy in cancer therapy. Interestingly, besides demonstration of some beneficial effects of novel anti-angiogenic compounds, recent data on the activity of already available drugs point to their potential application in anti-angiogenic therapy. Among these are the statins, the inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Statins are very efficient in the treatment of hypercholesterolemia in cardiovascular disorders; however, their effects are pleiotropic and some are not directly related to the inhibition of cholesterol synthesis. Some reports particularly highlight the pro-angiogenic effects of statins, which are caused by low, nanomolar concentrations and are regarded as beneficial for the treatment of cardiovascular diseases. On the other hand, the anti-angiogenic activities, observed at micromolar concentrations of statins, may be of special significance for cancer therapy. Those effects are caused by the inhibition of both proliferation and migration and induction of apoptosis in endothelial cells. Moreover, the statin-mediated inhibition of vascular endothelial growth factor synthesis, the major angiogenic mediator, may contribute to the attenuation of angiogenesis. It has been suggested that the anti-cancer effect of statins can be potentially exploited for the cancer therapy. However, several clinical trials aimed at the inhibition of tumor growth by treatment with very high doses of statins did not provide conclusive data. Herein, the reasons for those outcomes are discussed and the rationale for further studies is presented.
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影响因子：
5
作者：
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通讯作者：
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