Application of a gastric cancer cell line (MKN-28) for anti-adenovirus screening using the MTT method

Application of a gastric cancer cell line (MKN-28) for anti-adenovirus screening using the MTT method
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DOI:
10.1016/0166-3542(96)06966-5
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发表时间:
1996-07-01
期刊:
影响因子:
7.6
通讯作者:
DeClercq, E
DeClercq, E
中科院分区:
医学2区
文献类型:
--
作者:
Kodama, E;Shigeta, S;DeClercq, E

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我们建立了一种灵敏、准确的3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑(MTT)法筛选抗腺病毒药物的方法。MKN-28细胞,这是分化良好的胃腺癌细胞,用于腺病毒(ADV)感染,并检查了几种已建立的抗疱疹病毒剂的抗ADV活性。ADV-11是呼吸道和泌尿道感染的病原体。它经常引起免疫功能低下的宿主出血性膀胱炎。对ADV-11的1株实验室菌株和4株临床分离株进行了检查,发现对2-氨基-7-[(1,3-二羟基-2-丙氧基)甲基]嘌呤(S-2242)、(S)-9-(3-羟基-2-膦酰基甲氧基丙基)腺嘌呤[(S)-HPMPA]和(S)-1-(3-羟基-2-膦酰基甲氧基丙基)胞嘧啶[(S)-HPMC]敏感(按活性递减顺序)。另一方面,更昔洛韦和碘脱氧尿苷只有微弱的效果和硫酸葡聚糖是无效的。本研究结果表明,MKN-28细胞MTT法可用于抗ADV的筛选。证实了(S)-HPMPA和(S)-HPMPC的抗ADV活性,此外,S-2242是ADV-11的高效选择性抑制剂。
We established a sensitive and accurate method for screening of anti-adenovirus agents using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. MKN-28 cells, which are well-differentiated stomach adenocarcinoma cells, were used for adenovirus (ADV) infection and examined for the anti-ADV activities of several established anti-herpes virus agents. ADV-11 is the causative agent of respiratory and urinary infections. It frequently causes hemorrhagic cystitis in immunocompromised hosts. One laboratory strain and 4 clinical isolates of ADV-11 were examined, and found susceptible (in order of decreasing activity) to 2-amino-7-[(1,3-dihydroxy-2-propoxy)melhyl]purine (S-2242), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine[(S)-HPMPA], and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine[(S)-HPMC]. On the other hand, ganciclovir and iododeoxyuridine were only weakly effective and dextran sulfate was ineffective. Our findings indicate that the MTT assay using MKN-28 cells is applicable to anti-ADV screening. The anti-ADV activity of (S)-HPMPA and (S)-HPMPC was confirmed, and, furthermore, S-2242 emerged as a highly potent and selective inhibitor of ADV-11.