摘要
目的:探讨丙氧鸟苷(GCV)结合HSV-TK基因对人乳腺癌细胞系体外及体内杀伤作用及其产生的旁观者效应。方法:采用脂质体转染法将GINaTK载体转入包装细胞PA317。取病毒上清液感染人乳腺癌细胞,得到带有HSV-TK基因的TK细胞,并将其分别用于体外和体内实验。结果:体外实验结果显示,当TK细胞数占混合细胞10%时,低浓度(10μg/mL)的GCV就可将50%左右的肿瘤细胞杀死。体内实验结果显示GCV可明显抑制TK细胞在BALBPC小鼠体内的肿瘤形成。经GCV治疗后,肿瘤体积分别较对照组缩小约11.1%、30.6%和47.2%(P<0.01);实验组肿瘤组织与对照组相比存在明显的病理学改变。结论:逆转录病毒可介导HSV-TK基因转入小鼠乳腺癌细胞并获稳定表达,GCV结合HSV-TK基因在体内外对乳腺癌细胞均有杀伤作用,且存在明显的旁观者效应。
AIM： To study the killing effect and the bystander effect of gancyclovir （GCV） combining herpes simplex virus thymidine kinase （HSV-TK） gene therapy system on human breast cancer cells. METHODS： GINaTK retroviral vector containing HSV-TK gene was transduced into PA317 packaging cell by liposome transfection method. The human breast cancer cell line was infected by high titer viral supematant. MA782/SS-8102/TK cells and MA782/5S-8102 cells were used in in vitro and in vivo study. RESISTS： Experimental results revealed that in in vitro study when the cell population ratio of MA782/5S-8102/TK cells reached 10% the tumor cell-killing proportion was almost 50%, in in vivo study GCV could suppress tumor formation of the MA782/5S-8102/TK cells. After treated with GCV, the median tumor volume of mice implanted with MA782/SS-8102/TK ＋ MA782/5S-8102 （1 ： 9） group MA782/5S-8102/TK ＋ MA782/5S-8102 （1： 1） and MA782/5S-8102/TK cellswas respectively decreased by 11.1% （P 〈 0.01 ）, 30.6% and 47.2% compared with the control tumors. Tumors treated with GCV revealed different histopathologieal features compared with the control tumors. CONCLUSION： The HSV-TK gene could be tmnsdueted into human breast cancer line under the mediation of retrovirus and be stable expressed, HSV-TK/GCV gene therapy system could improve the antitumoral efficiency. The bystander effect could be observated in HSVTK/GCV system in in vitro and in vivo.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2008年第8期856-859,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
青海省重点科技攻关项目(2006-N-175)
关键词
丙氧鸟苷
单纯疱疹病毒胸苷激酶
乳腺癌
gancyclovir
herpes simplex virus thymidine kinase （HSV-TK）
breast cancer
