Zhou Xian-Long, Shi Yu-Lu, Li Xiong
Emergency Center, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.
Medical College of Wuhan University, Wuhan, Hubei 430072, P.R. China.
Exp Ther Med. 2014 Oct;8(4):1159-1163. doi: 10.3892/etm.2014.1877. Epub 2014 Aug 4.
The aim of the present study was to investigate the effect of the ultrasound-targeted microbubble destruction mediated (UTMD) herpes simplex virus-thymidine kinase (HSV-TK) and ganciclovir (GCV) system on ovarian cancer (OC). This study was conducted between June and December 2012 in the Animal Biosafety Level III Laboratory of Wuhan University. Mice with OC were randomly divided into four groups: i) HSV-TK plus microbubbles (MBs) plus ultrasound (US) (n=15); ii) HSV-TK plus US (n=15); iii) HSV-TK (n=15); and iv) phosphate-buffered saline (n=15). The inhibitory effect and survival time in the experimental groups were compared with those in the control group. The TK protein expression was detected by western blot analysis. Tumor cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and caspase-3 activity analysis. The data showed that the efficiency of HSV-TK gene transfection and the tumor inhibitory effects were significantly increased in the HSV-TK plus MBs plus US group compared with those in the control group (P<0.01). UTMD-mediated HSV-TK treatment has also improved the rat survival rate (P<0.01). In conclusion, UTMD can effectively transfect the HSV-TK gene into target tissues and exert a significant inhibitory effect on OC in mice.
本研究旨在探讨超声靶向微泡破坏介导(UTMD)的单纯疱疹病毒胸苷激酶(HSV-TK)和更昔洛韦(GCV)系统对卵巢癌(OC)的影响。本研究于2012年6月至12月在武汉大学动物生物安全三级实验室进行。将患有卵巢癌的小鼠随机分为四组:i)HSV-TK加微泡(MBs)加超声(US)组(n = 15);ii)HSV-TK加超声组(n = 15);iii)HSV-TK组(n = 15);iv)磷酸盐缓冲液组(n = 15)。将实验组的抑制效果和生存时间与对照组进行比较。通过蛋白质免疫印迹分析检测TK蛋白表达。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记和caspase-3活性分析检测肿瘤细胞凋亡。数据显示,与对照组相比,HSV-TK加MBs加US组的HSV-TK基因转染效率和肿瘤抑制效果显著提高(P<0.01)。UTMD介导的HSV-TK治疗也提高了大鼠的生存率(P<0.01)。总之,UTMD可以有效地将HSV-TK基因转染到靶组织中,并对小鼠卵巢癌发挥显著的抑制作用。