Treatment of human hepatocellular carcinoma by the oncolytic herpes simplex virus G47delta.
Treatment of human hepatocellular carcinoma by the oncolytic herpes simplex virus G47delta.
复制标题
溶瘤单纯疱疹病毒 G47delta 治疗人肝细胞癌
DOI：
10.1186/s12935-014-0083-y
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发表时间：
2014
影响因子：
5.8
通讯作者：
Liu R
中科院分区：
文献类型：
--
作者：
Wang J;Xu L;Zeng W;Hu P;Zeng M;Rabkin SD;Liu R
背景溶瘤性单纯疱疹病毒（oncolytic herpes simplex virus，HSV）能在癌细胞内复制并杀死癌细胞，而不影响癌旁正常组织。肝细胞癌（HCC）是最常见和致命的癌症之一，特别是在第三世界国家。在这项研究中，第三代溶瘤HSV G47Δ在不同的人HCC细胞系和永生化的人肝细胞系中研究了细胞毒性。方法用G47Δ以不同的感染复数（MOI）感染HepG 2、HepB、SMMC-7721、BEL-7404、BEL-7405人肝癌细胞系和HL-7702人肝永生化细胞系。测定感染细胞的活力，并通过LacZ表达的X-gal染色鉴定G47Δ复制。两个皮下（s.c.）还在Balb/c裸小鼠中建立HCC的HCC肿瘤模型，其瘤内（i. t.）用G47Δ或模拟病毒处理。肿瘤体积和小鼠的生存时间被document.Results95%以上的HepG 2，Hep 3B，和SMMC-7721肝癌细胞被杀死后5天感染的MOI的0.01。对于HL-7702人肝永生化细胞，在MOI为0.01的感染后第5天，100%的细胞被杀死。BEL-7404 HCC细胞系较不敏感，在MOI为0.01的感染后第5天，约70%的细胞被杀死。而BEL-7405肝癌细胞是最不敏感的，只有30%的细胞被杀死。SMMC-7721和BEL-7404细胞均形成侵袭性sc肿瘤模型。结论G47 Δ在低MOI条件下能有效杀伤人肝癌细胞和永生化肝细胞株。肿瘤内注射G47Δ可以诱导治疗效果，并延长皮下（s.c.）肿瘤的因此，G47Δ可用作HCC的新治疗剂。
BackgroundOncolytic herpes simplex virus (HSV) can replicate in and kill cancer cells while sparing the adjacent normal tissue. Hepatocellular carcinoma (HCC) is amongst the most common and lethal cancers, especially in Third World countries. In this study, the cytotoxicity of a third-generation oncolytic HSV, G47Δ, was investigated in different human HCC cell lines and in an immortalized human hepatic cell line. Additionally, subcutaneous models of HCC were established to evaluate thein vivoanti-tumor efficacy of G47Δ.MethodsThe HepG2, HepB, SMMC-7721, BEL-7404, and BEL-7405 human HCC cell lines and the HL-7702 human hepatic immortalized cell lines were infected with G47Δ at different multiplicities of infection (MOIs). The viability of infected cells was determined, and the G47Δ replication was identified by X-gal staining for LacZ expression. Two subcutaneous (s.c.) HCC tumor models of HCC were also established in Balb/c nude mice, which were intratumorally(i.t.) treated with either G47Δ or mock virus. Tumor volume and mouse survival times were documented.ResultsMore than 95% of the HepG2, Hep3B,and SMMC-7721 HCC cells were killed on by day 5 after infection with a MOI’s of 0.01. For the HL-7702 human hepatic immortalized cells, 100% of the cells were killed on by day 5 after infection with a MOI’s of 0.01. The BEL-7404 HCC cell line was less susceptible with about 70% cells were killed by day 5 after infection with a MOI’s of 0.01. Whereas the BEL-7405 HCC cells were the least susceptible, with only 30% of the cells were killed. Both the SMMC-7721 and BEL-7404 cells form aggressive sc tumor models. G47Δ replicates in the tumors, such that most of the tumors regressed after the G47Δ-treatment, and treated tumor-bearing mice survived much longer than the control animals.ConclusionsG47Δ effectively kills human HCC cells and an immortalized hepatic cell line at low MOI. Intra-tumor injection of G47Δ can induce a therapeutic effect and prolong the survival of treated mice bearing SMMC-7721 and BEL-7404 subcutaneously (s.c.) tumors. Thus, G47Δ may be useful as a novel therapeutic agent for HCC.
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影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
DOI：
10.1111/j.1749-6632.2002.tb04090.x
发表时间：
2002-01-01
期刊：
HORMONE-RELATED TUMORS: NOVEL APPROACHES TO PREVENTION AND TREATMENT
影响因子：
--
作者：
Montalto, G;Cervello, M;Castagnetta, LAM
通讯作者：
Castagnetta, LAM
影响因子：
4.2
作者：
Delman, KA;Bennett, JJ;Fong, Y
通讯作者：
Fong, Y
影响因子：
6.4
作者：
Bennett, JJ;Delman, KA;Fong, YM
通讯作者：
Fong, YM
影响因子：
2.5
作者：
Marrero, JA
通讯作者：
Marrero, JA