Olmesartan potentiates the anti-angiogenic effect of sorafenib in mice bearing Ehrlich's ascites carcinoma: role of angiotensin (1-7).
Olmesartan potentiates the anti-angiogenic effect of sorafenib in mice bearing Ehrlich's ascites carcinoma: role of angiotensin (1-7).
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DOI：
10.1371/journal.pone.0085891
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Moustafa YM
中科院分区：
文献类型：
--
作者：
Abd-Alhaseeb MM;Zaitone SA;Abou-El-Ela SH;Moustafa YM
局部肾素-血管紧张素系统存在于各种恶性肿瘤组织中；这表明主要的效应肽血管紧张素II可能是肿瘤生长的关键因素。血管紧张素II型1受体阻滞剂抗血管生成作用的潜在机制有待进一步研究。本研究旨在研究奥美沙坦单独或与血管紧张素（1-7）激动剂或血管紧张素（1-7）拮抗剂索拉非尼（sorafenib）联合使用对Ehrlich腹水癌小鼠的抗血管生成作用。采用皮内注射埃利希腹水癌细胞诱导小鼠发生肿瘤。用肿瘤椎间盘评估微血管密度；血清血管内皮生长因子（VEGF）和胰岛素样生长因子I （IGF-I）水平；以及它们的肿瘤内受体，VEGF受体-2和igf - 1受体。在接种后21 d的处理过程中测定所有参数。奥美沙坦单药治疗及其与索拉非尼联合治疗可显著降低微血管密度、血清中VEGF和IGF-I水平及其肿瘤内受体。此外，奥美沙坦（30mg /kg）与血管紧张素（1-7）激动剂联合使用可降低微血管密度、血清IGF-I水平及其肿瘤内受体水平。综上所述，奥美沙坦降低了血管生成标志物IGF-I和VEGF的水平，并以剂量依赖的方式下调了它们的肿瘤内受体的表达，这些作用依赖于血管紧张素（1-7）受体。这些结果表明，奥美沙坦是索拉非尼治疗癌症的一种有希望的辅助药物。
Local renin-angiotensin systems exist in various malignant tumor tissues; this suggests that the main effector peptide, angiotensin II, could act as a key factor in tumor growth. The underlying mechanisms for the anti-angiogenic effect of angiotensin II type 1 receptor blockers need to be further evaluated. The present study was carried out to investigate the anti-angiogenic effect of olmesartan alone or in combination with sorafenib, an angiotensin (1–7) agonist or an angiotensin (1–7) antagonist in Ehrlich's ascites carcinoma-bearing mice. The tumor was induced by intradermal injection of Ehrlich's ascites carcinoma cells into mice. Tumor discs were used to evaluate the microvessel density; the serum levels of vascular endothelial growth factor (VEGF) and serum insulin-like growth factor I (IGF-I); and their intratumoral receptors, VEGF receptor-2 and IGF-I receptor, respectively. All parameters were determined following the treatment course, which lasted for 21 days post-inoculation. Monotherapy with olmesartan and its combination with sorafenib resulted in a significant reduction in microvessel density and serum levels of VEGF and IGF-I, as well as their intratumoral receptors. In addition, the combination of olmesartan (30 mg/kg) with an angiotensin (1–7) agonist reduced the microvessel density, IGF-I serum levels and the levels of its intratumoral receptor. In conclusion, olmesartan reduced the levels of the angiogenesis markers IGF-I and VEGF and down-regulated the intratumoral expression of their receptors in a dose-dependent manner, and these effects were dependent on the angiotensin (1–7) receptor. These results suggest that olmesartan is a promising adjuvant to sorafenib in the treatment of cancer.
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影响因子：
51.1
作者：
Key, Timothy J.;Appleby, Paul N.;Reeves, Gillian K.;Roddam, Andrew W.
通讯作者：
Roddam, Andrew W.
影响因子：
11.5
作者：
Kosugi, M;Miyajima, A;Murai, M
通讯作者：
Murai, M
影响因子：
2.9
作者：
Gong, Qiaoke;Davis, Molly;Arafat, Hwyda A.
通讯作者：
Arafat, Hwyda A.
DOI：
10.1016/s0006-291x(02)00496-5
发表时间：
2002-06-07
影响因子：
3.1
作者：
Fujita, M;Hayashi, I;Majima, M
通讯作者：
Majima, M
影响因子：
4.2
作者：
Funao, Kiyoaki;Matsuyama, Masahide;Yoshimura, Rikio
通讯作者：
Yoshimura, Rikio