转基因溶瘤性单纯疱疹病毒对人类乳腺癌的治疗作用  

Oncolytic herpes simplex virus vectors for the treatment of human breast cancer

作　　者：王佳妮[1] 刘仁斌[1] 李俊杰[1] Mohamed Abdalwali.Thabit Samuel D.Rabkin 

机构地区：[1]中山大学附属第三医院乳腺疾病诊治中心,广州510630 [2]美国哈佛大学麻省总医院分子外科实验室,波士顿02114

出　　处：《中华乳腺病杂志（电子版）》2009年第6期34-37,共4页Chinese Journal of Breast Disease(Electronic Edition)

基　　金：国家自然科学基金资助项目(30672410);广州市科技局国际合作项目(2007Z3-I0021)

摘　　要：目的通过观察溶瘤性单纯疱疹病毒(HSV)载体G47Δ对人类乳腺癌细胞系SK-BR-3、MDA-MB-453和MDA-MB-231的细胞毒效应,探讨其对人乳腺癌的治疗作用。方法体外培养人乳腺癌细胞SK-BR-3、MDA-MB-453和MDA-MB-231,将G47Δ按不同滴度(MOI)加入培养液中,每天观察细胞的生长状态。G47Δ含有LacZ基因,其在被感染细胞中的表达可用X-gal染色检测。结果较低MOI(0.01)的G47Δ对SK-BR-3和MDA-MB-453具有较高的毒性,但对MDA-MB-231没有杀伤作用。在MOI=0.01的实验组,感染病毒后第5天,超过90%的SK-BR-3和MDA-MB-453细胞已被杀灭;但在MOI=0.01组及MOI=0.10组,MDA-MB-231感染G47Δ后细胞数量与对照组相比均无差异。采用X-gal染色证实了病毒在癌细胞中复制和传播。结论近期构建的HSV载体-G47Δ可有效杀灭人乳腺癌细胞SK-BR-3和MDA-MB-453,但未显示出对MDA-MB-231的影响。G47Δ的有效性及缺陷为新型溶瘤性单纯疱疹病毒G47Δ用于乳腺癌治疗的临床试验提供有力依据,但其应用尚需进一步研究。Objective To investigate the efficacy of herpes simplex virus （HSV） vector, G47△ for the treatment of the human breast cancer through the observation of its cytotoxicity on three human breast cancer cell lines, SK-BR-3, MDA-MB-453 and MDA-MB 231. Methods Human breast cancer SK BR-3, MDA-MB-453 and MDA-MB-231 cells were cultured and inoculated with G47△ of different multiplicities of infection （MOI）. The cytotoxicity was observed every day. G47△ contained the LacZ gene, whose expression in infected cells was detected with X gal histochemistry. Results G47△ was highly cytotoxic for SK-BR-3 and MDA MB-453 cells in vitro at very low MOI （0.01）, but no efficiency was observed in MDA-MB-231 cells. X-gal staining of infected tumor cells in vitro illustrated the replication and spread of the virus. In the MOI=0.01 group, on the fifth day after infection, more than 90% SK-BR-3 and MD-MB-453 cells were killed, but after MDA-MB-231 was infected, in the MOI=0.01 and MOI= 0. 10 groups, the cell number was similar to the mock. Conclusions Recently constructed oncolytic HSV vector G47△ was effective at killing human breast cancer SK-BR-3 and MDA-MB-453 cells in vitro, but did not influence the growth of MDA-MB-231. The efficiency and deficiency of this novel cancer therapy warrants further investigation and consideration of clinical application.

关 键 词：癌症治疗 单纯疱疹病毒 溶瘤性病毒 基因治疗 乳腺肿瘤 

分 类 号：R737.9[医药卫生—肿瘤]