Captopril as a Potential Inhibitor of Lung Tumor Growth and Metastasis
Captopril as a Potential Inhibitor of Lung Tumor Growth and Metastasis
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DOI：
10.1196/annals.1414.011
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Petroianu, Georg
中科院分区：
文献类型：
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作者：
Attoub, Samir;Gaben, Anne Marie;Petroianu, Georg
肺癌是世界上最常见的癌症，90%的患者死于这种疾病。血管紧张素转换酶（ACE）抑制剂被广泛用作抗高血压药物，并且已经表明它们可以降低某些癌症的风险，尽管现有的数据相互矛盾。因此，我们研究了血管紧张素转换酶抑制剂，卡托普利，在无胸腺小鼠注射高度致瘤性LNM 35人肺细胞作为异种移植物的抗癌活性。使用该模型，我们证明了每天IP给予Captopril（2.8mg/小鼠）3周导致肿瘤生长（58%，P < 0.01）和淋巴结转移（50%，P = 0.088）的显著减少。开搏通治疗对动物行为和体重没有不良影响。为了确定巯甲丙脯酸抑制肿瘤生长的机制，我们研究了这种药物对细胞增殖、凋亡和血管生成的影响。免疫组织化学分析表明，卡托普利治疗显着减少增殖细胞（Ki.- 67)在肿瘤样品中，但与肿瘤血管生成（CD 31）的抑制无关。使用细胞活力和荧光激活细胞分选分析测试，我们证明，卡托普利抑制LNM 35细胞的活力，诱导凋亡，提供洞察其抗肿瘤活性的机制。鉴于这些实验结果，我们得出结论，卡托普利可能是一个有前途的选择，用于治疗肺癌。
Lung cancer is the most common form of cancer in the world, and 90% of patients die from their disease. The angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents, and it has been suggested that they decrease the risk of some cancers, although available data are conflicting. Accordingly, we investigated the anticancer activity of the ACE inhibitor, captopril, in athymic mice injected with highly tumorigenic LNM35 human lung cells as xenografts. Using this model, we demonstrated that daily IP administration of captopril (2.8 mg/mouse) for 3 weeks resulted in a remarkable reduction of tumor growth (58%, P < 0.01) and lymph node inetastasis (50%, P = 0.088). There were no undesirable effects of captopril treatment on animal behavior and body weight. In order to determine the mechanism by which captopril inhibited tumor growth, we investigated the impact of this drug on cell proliferation, apoptosis, and angiogenesis. Immunohistochemical analysis demonstrated that captopril treatment significantly reduced the number of proliferating cells (Ki.-67) in the tumor samples but was not associated with inhibition of tumor angiogenesis (CD31). Using cell viability and fluorescent activated cell sorting analysis tests, we demonstrated that captopril inhibited the viability of LNM35 cells by inducing apoptosis, providing insight about the mechanisms underlying its antitumorigenic activities. In view of these experimental findings, we conclude that captopril could be a promising option for the treatment of lung cancer.