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新城疫病毒株 AF2240 和 V4-UPM 在体内对鼠髓单核白血病的抗白血病活性。

Anti-leukemic activity of Newcastle disease virus strains AF2240 and V4-UPM in murine myelomonocytic leukemia in vivo.

机构信息

Department of Biotechnology, University Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia.

出版信息

Leuk Res. 2012 May;36(5):634-45. doi: 10.1016/j.leukres.2011.11.001. Epub 2011 Nov 30.

Abstract

Newcastle disease virus (NDV) is a member of the Paramyxoviridae that has caused severe economic losses in poultry industry worldwide. Several strains of NDV were reported to induce cytolysis to cancerous cell lines. It has prompted much interest as anticancer agent because it can replicate up to 10,000 times better in human cancer cells than in most normal cells. In this study, two NDV strains, viserotropic-velogenic strain AF2240 and lentogenic strain V4-UPM, showed cytolytic activity and apoptosis induction against Mouse myelomoncytic leukemia (WEHI 3B). The cytolytic effects of NDV strains were determined using microtetrazolium (MTT) assay. The cytolytic dose - fifty percent (CD(50)) were 2 and 8HAU for AF2240 and V4-UPM strains, respectively. Cells treated with NDV strains showed apoptotic features compared to the untreated cells under fluorescence microscope. NDV induced activation of caspase-3 and DNA laddering in agarose gel electrophoresis which confirmed the apoptosis. The anti-leukemic activity of both strains was evaluated on myelomoncytic leukemia BALB/c mice. The results indicated that both NDV strains significantly decreased liver and spleen weights. It also decreased blasts cell percentage in blood, bone marrow and spleen smears of treated mice (p<0.05). Histopathological studies for spleen and liver confirmed the hematological results of blood and bone marrow. From the results obtained, the exposure to both NDV stains AF2240 and V4-UPM showed similar results for Ara-c. In conclusion NDV strains AF2240 and V4-UPM can affect WEHI 3B leukemia cells in vitro and in vivo.

摘要

新城疫病毒(NDV)是副粘病毒科的一员,在全球范围内给家禽业造成了严重的经济损失。据报道,NDV 的几种毒株能诱导癌细胞系发生细胞溶解。由于其在人类癌细胞中的复制能力比大多数正常细胞高出 10000 倍,因此它作为抗癌药物引起了广泛的兴趣。在本研究中,两种 NDV 株,亲嗜性强毒力株 AF2240 和低毒力株 V4-UPM,对鼠髓单核白血病(WEHI 3B)显示出细胞溶解活性和凋亡诱导作用。用微量四唑盐(MTT)测定法测定 NDV 株的细胞溶解作用。AF2240 和 V4-UPM 株的细胞溶解剂量-五十(CD(50))分别为 2 和 8HAU。与未处理的细胞相比,用 NDV 株处理的细胞在荧光显微镜下显示出凋亡特征。NDV 诱导 caspase-3 的激活和琼脂糖凝胶电泳中的 DNA 梯状,证实了凋亡的发生。两种毒株的抗白血病活性均在髓单核白血病 BALB/c 小鼠中进行了评价。结果表明,两种 NDV 株均显著降低了肝和脾的重量。它还降低了治疗小鼠血液、骨髓和脾涂片中的原始细胞百分比(p<0.05)。脾和肝的组织病理学研究证实了血液和骨髓的血液学结果。从获得的结果来看,暴露于两种 NDV 株 AF2240 和 V4-UPM 对阿糖胞苷表现出相似的结果。总之,NDV 株 AF2240 和 V4-UPM 可在体外和体内影响 WEHI 3B 白血病细胞。

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