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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >FTY720 induced Bcl-associated and Fas-independent apoptosis in human renal cancer cells in vitro and significantly reduced in vivo tumor growth in mouse xenograft.
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FTY720 induced Bcl-associated and Fas-independent apoptosis in human renal cancer cells in vitro and significantly reduced in vivo tumor growth in mouse xenograft.

机译：FTY720体外诱导人肾癌细胞中Bcl相关和Fas依赖性凋亡，并显着降低小鼠异种移植物中体内肿瘤的生长。

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BACKGROUND: A unique immunosuppressant, FTY720, selectively induces apoptosis in activated lymphocytes, but not in other hematopoietic cells. The potential that this unique mechanism could provide anticancer potential by inducing apoptosis in the human renal cancer cell line, ACHN, which is resistant to cisplatin, and its molecular pathway was investigated. MATERIALS AND METHODS: The difference in drug susceptibility to FTY720 between cancer cells and non-cancer cells was examined by MTT assay and flow cytometry. Apoptosis assay, including TUNEL staining, electron microscopy and DNA electrophoresis, was performed and the molecular pathway of FTY720 was evaluated by real time RT-PCR and Western blot. The in vivo effect of FTY720 was evaluated using a murine zenograft model. RESULTS: The susceptibility to FTY720 was significantly higher in ACHN cancer cells than in normal renal tubular cells (HK-2) at a concentration of less than 30 microM, while the susceptibility to cisplatin was even higher in HK-2 than in ACHN. Cancer cells treated with FTY720 showed findings typical of apoptosis with highly condensed nuclear chromatin and fragmented nuclei. The molecular analysis revealed that FTY720-induced apoptosis was mediated by a Fas-independent, Bcl-associated signal transduction pathway, and that inhibition of extracellular signal-regulated kinase (ERK) activity was involved in its underlying mechanism of action. FTY720 treatment significantly prevented in vivo tumor growth without any severe adverse reactions, while cisplatin treatment did not inhibit tumor growth despite exhibiting severe side-effects. CONCLUSION: FTY720 may be a promising candidate for a new anticancer therapy of renal cancer.
机译：背景：独特的免疫抑制剂FTY720选择性诱导活化淋巴细胞的凋亡，但不诱导其他造血细胞的凋亡。这种独特的机制可能通过诱导对顺铂耐药的人肾癌细胞株ACHN的凋亡来提供抗癌潜力，并研究了其分子途径。材料与方法：用MTT法和流式细胞仪检测癌细胞与非癌细胞对FTY720的药敏性差异。进行细胞凋亡分析，包括TUNEL染色，电子显微镜和DNA电泳，并通过实时RT-PCR和Western blot评估FTY720的分子途径。使用鼠异种移植模型评估FTY720的体内作用。结果：在小于30 microM的浓度下，ACHN癌细胞对FTY720的敏感性显着高于正常肾小管细胞（HK-2），而HK-2的顺铂敏感性甚至比ACHN高。用FTY720处理的癌细胞显示出典型的凋亡现象，并带有高度浓缩的核染色质和碎裂的核。分子分析表明，FTY720诱导的细胞凋亡是由Fas独立的，Bcl相关的信号转导途径介导的，而细胞外信号调节激酶（ERK）活性的抑制与其潜在的作用机制有关。 FTY720治疗显着阻止了体内肿瘤的生长，而没有任何严重的不良反应，而顺铂治疗尽管显示出严重的副作用，但并未抑制肿瘤的生长。结论：FTY720可能是一种新的肾癌抗癌治疗方法。

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