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MDAMB-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,G47Δfor 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,MDAMB-453 and MDA-MB-231 cells were cultured and inoculated with G47Δof different multiplicities of infection(MOI).The cytotoxicity was observed every day.G47Δ contained the LacZ gene,whose expression in infected cells was detected with X-gal histochemistry.

Results

G47Δwas 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 MDA-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 G47Δwas 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.