超声微泡靶向破坏介导HSV-TK／GCV抑制BALB／c-nu小鼠卵巢癌的实验研究  

Inhibitory effects of ultrasound-targeted microbubble destruction mediated HSV-TK/GCV system on ovarian cancer in BALB/c-nu mice

作　　者：周贤龙[1] 施余露[1] 李雄[1] 汪迎晖[1] 黎萍[1] 王薇[1] 

机构地区：[1]武汉大学中南医院超声科,430071

出　　处：《中华超声影像学杂志》2012年第10期897-901,共5页Chinese Journal of Ultrasonography

基　　金：湖北省自然科学基金项目（2008CDB149）

摘　　要：目的探讨超声微泡靶向破坏介导下HSV-TK基因联合更昔洛韦对裸鼠卵巢癌的杀伤效应。方法挑选成功种植卵巢癌细胞且状态良好的雌性BALB／c-nu小鼠40只，随机分为4组：A组，HsV-TK＋超声微泡（MBs）＋超声辐射（US）组；B组，HSV-TK＋超声辐射（Us）组；C组，HSV-TK组；D组，磷酸盐缓冲液（PBS）组。分别利用Western-Blot和realtimeRT-PCR检测各组瘤体组织内TK蛋白和mRNA的表达，TUNEL法检测不同组的肿瘤细胞凋亡，并比较各组之间的肿瘤生长状况及裸鼠生存时间。结果A组TK蛋白、mRNA表达及肿瘤细胞凋亡率高于其他各组（P〈O．05），平均肿瘤体积A组显著低于其他各组（P〈0．05），但生存时间上A组同其他各组之间差异并无统计学意义。结论超声微泡靶向破坏介导HSV-TK联合更昔洛韦可促进裸鼠卵巢癌细胞的凋亡，并抑制肿瘤生长速度，但短期观察并不能延长裸鼠生存时间。Objective To investigate the anti-tumor effect of ultrasound-targeted microbubble destruction （UTMD） mediated herpes simplex virus thymedine kinase （HSV-TK） on mice ovarian cancer. Methods Forty female BALB/c-nu mice were randomly divided into four groups after the models of subcutaneous transplantation tumors were established： （A） HSV-TK ＋ Microbubbles ＋ Ultrasound （HSV- TK＋ MBs ＋ US）; （B） HSV-TK ＋ Ultrasound （HSV-TK ＋ US）; （C） HSV-TK; （D） PBS. The TK protein and mRNA expression were separately detected by western-blot and real time RT-PCR. TUNEL staining was used to detect the tumor cell apoptosis. The inhibition rates and survival time of the animals were compared among all groups. Results The HSV-TK gene transfection efficacy and tumor inhibitory effect of HSV-TK on mice transplantable tumor in group A （HSV-TK ＋ MBs ＋ US） were significantly improved compared with group B （HSV-TK ＋ US） ,group C （HSV-TK） and group D （PBS） （P〈0.05）. However,group A has no significant difference （P〈0.05） with other groups in improving the survival time of tumor-bearing mice. Conclusions Ultrasound-targeted microbubble destruction can effectively transfect HSV-TK gene into target tissues and play a significant inhibition effect on ovarian cancer in mice. However,this new method is not able to improve the survival time of mice for a short-term observation.

关 键 词：超声检查 微气泡 基因疗法 卵巢肿瘤 

分 类 号：R737.31[医药卫生—肿瘤]