Antitumor activity of the antimicrobial peptide Magainin II against bladder cancer cell lines
Antitumor activity of the antimicrobial peptide Magainin II against bladder cancer cell lines
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DOI：
10.1016/j.eururo.2005.12.043
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发表时间：
2006-07-01
期刊：
影响因子：
23.4
通讯作者：
Stoeckle, Michael
中科院分区：
文献类型：
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作者：
Lehmann, Jan;Retz, Margitta;Stoeckle, Michael
目的：爪蟾抗菌肽II是一个具有抗菌活性的多肽家族。最近的研究还报道了爪蟾抗菌肽对多种癌细胞系和肿瘤小鼠模型的显著抗肿瘤作用。在这项研究中，我们评估了爪蟾抗菌肽II在膀胱肿瘤细胞和正常成纤维细胞中的细胞毒性和抗增殖能力。通过WST-1-、溴脱氧尿苷（BrdU）-和乳酸脱氢酶（LDH）比色分析，在三种膀胱癌细胞系中定量爪蟾抗菌肽11的抗增殖和细胞毒性作用（RT 4、647 V和486 P）和鼠成纤维细胞系3 T3以及来自人成纤维细胞的原代培养物中。测定各试验的中位抑制浓度（IC 50）值，代表细胞活力降低50%时的浓度。扫描电镜观察爪蟾抗菌肽11对膀胱癌细胞和成纤维细胞的形态学影响。结果：爪蟾抗菌肽11对膀胱癌细胞的增殖有抑制作用，且呈剂量依赖性。爪蟾抗菌肽11对所有膀胱癌细胞系的平均IC 50对于WST-1测定为198.1 μ M（范围，52.4-484.03 μ M），对于BrdU测定为75.2 μ M（范围，31.0-135.3 μ M）。正常鼠和人成纤维细胞系不受爪蟾抗菌肽II的影响，并且在测试的爪蟾抗菌肽II浓度下无法测定其IC 50。LDH释放增加，在所有膀胱肿瘤细胞系的存在下，爪蟾抗菌肽II，而正常的成纤维细胞显示没有细胞溶解。扫描电镜显示，致命的膜穿孔的肽孔形成在膀胱癌细胞，但不是在fibroblast.Conclusion：爪蟾抗菌肽II发挥细胞毒性和抗增殖作用的孔形成在膀胱癌细胞，但对正常小鼠或人成纤维细胞没有影响。爪蟾抗菌肽II可能提供一种新的治疗策略，在膀胱癌的治疗与潜在的低细胞毒性作用的nor-Mal细胞。(c)2005年欧洲泌尿外科协会。Elsevier B. V.出版，保留所有权利。
Objective: Magainin II belongs to a family of antimicrobial peptides and has been shown to exhibit antibiotic activity in a wide range of organisms. Recent studies have also reported a significant antitumor effect of magainin if against various cancer cell lines and tumor mice models. In this study, we evaluated the cytotoxic and antiproliferative potency of magainin II in bladder tumor cells and normal fibroblasts.Methods: The antiproliferative and cytotoxic effect of magainin 11 was quantified by colorimetric WST-1-, bromodeoxyuridine (BrdU)-, and lactic dehydrogenase (LDH) assays in three bladder cancer cell lines (RT4, 647V, and 486P) and in the murine fibroblast cell line 3T3 as well as in a primary culture from human fibroblasts. The median inhibitory concentration (IC50) values were determined for each assay, representing the concentration at which cell viability was reduced by 50%. Scanning electron microscopy (SEM) was used to visualize the morphologic effects of magainin 11 on bladder tumor cells and fibroblasts.Results: Magainin 11 inhibited cell proliferation of bladder cancer cells in a dose-dependent manner. The average IC50 of magainin 11 against all bladder cancer cell lines was 198.1 mu M (range, 52.4-484.03 mu M) for the WST-1 assay and 75.2 mu M (range, 31.0-135.3 mu M) for the BrdU assay. The normal murine and human fibroblast cell lines were not affected by magainin II and their IC50 could not be determined at the concentrations of magainin II tested. LDH release was increased in all bladder tumor cell lines in the presence of magainin II, whereas normal fibroblasts showed no cell lysis. SEM demonstrated lethal membrane perforation by peptide pore formation in bladder cancer cells, but not in fibroblasts.Conclusion: Magainin II peptide exerts cytotoxic and antiproliferative efficacy by pore formation in bladder cancer cells but has no effect on normal murine or human fibroblasts. Magainin II may offer a novel therapeutic strategy in the treatment of bladder cancer with potentially low cytotoxic effects on nor-Mal cells. (c) 2005 European Association of Urology. Published by Elsevier B.V. All rights reserved.