摘要
目的 观察Scopadulciol（SDC）在人端粒酶逆转录酶（hTERT）启动子调控腺病毒介导的单纯疱疹病毒胸腺激酶基因/丙氧鸟苷（HSV-tk/GCV）自杀基因系统对裸鼠膀胱癌的体内杀伤作用中的增效作用.方法 首先建立人膀胱癌裸鼠皮下移植瘤模型,当肿瘤生长至直径约为6mm或体积为100 mm3时,随机分为4组,每组4只.A组为Ad-hTERT-HSV/tk＋ GCV＋ SDC组：于第1、5、10天每只裸鼠肿瘤内注射Ad-hTERT-HSV/tk（1×109 pfu）0.1 ml,第2天开始腹腔注射GCV（2.0 mg/d）×15 d和SDC（1 mg/d）×15 d.B组为Ad-hTERT-HSV/tk＋ GCV组：注射Ad-hTERT-HSV/tk、GCV同A组.C组为Ad-hTERT-HSV/tk＋ SDC组：注射Ad-hTERT-HSV/tk、SDC同A组.D组为对照组：裸鼠肿瘤内及腹腔内仅注射磷酸盐缓冲液（PBS）.自注射药物开始,每7d用圆规和游标卡尺测量肿瘤大小,计算肿瘤的体积,描绘肿瘤的生长曲线,共观察6周.另作4组治疗同上,2周后停止治疗,记录各组裸鼠的存活期,以观察对照组和治疗组存活期的改变.结果 单纯Ad-hTERT-tk/SDC（C组）及对照组（D组）对肿瘤生长无抑制或促进作用；而经过Ad-hTERT-tk/GCV治疗的B组裸鼠,显示出对肿瘤有抑制作用,其体积低于C、D组（P＜0.01）,Ad-hTERT-HSV/tk/GCV＋ SDC治疗的A组抑制肿瘤作用更为明显,比较B组有明显的增强作用,与B组比较差异有统计学意义（P＜0.01）,与C、D两组比较差异有统计学意义（P＜0.01）.B、C、D各组荷瘤裸鼠的平均存活期分别为（54.0±3.2）、（50.2±3.0）和（49.7±3.7）d,而A组荷瘤裸鼠平均存活期延长至（73.0±5.6）d,与其余各照组比较差异有统计学意义（P＜0.01）.结论 Scopadulciol对胸腺激酶依赖的GCV阻断膀胱癌进展有一定的增效作用,将Scopadulciol与我们构建的具有肿瘤特异性的重组腺病毒Ad-hTERT-HSV-tk以及GCV联合应用于人膀胱癌裸鼠皮下移植瘤模型的治疗,具有明显增效作用.
Objective To investigate the enhanced effect of Scopadulciol （SDC） in treating human 253J carcinoma transplanted subcutaneously in nude mice by thymidine kinase （TK）-dependent ganciclovir.Methods Human 253J carcinoma model transplanted subcutaneously in nude mice was established firstly,followed by the therapy of the different combinations of Ad-hTERT-HSV-tk,GCV and SDC when the tumors＇ diameter was up to 10 mm or the volume up to 100 mm3.They were randomly divided into 4 groups （n =4）：group A （Ad-hTERT-HSV/tk,GCV,SDC）,intratumor injection of Ad-hTERT-HSV/tk l × 109（pfu） （0.1 ml） at 1st,5th,and 10th day,intraperitoneal injection of GCV 2.0 mg,and SDC 1 mg at day 2 to day 15; group B （Ad-hTERT-HSV/tk,GCV）,injection of Ad-hTERT-HSV/tk and GCV same as group A; group C （Ad-hTERT-HSV/tk,SDC） group,injection of Ad-hTERT-HSV/tk and SDC same as group A.Group D was the control group：the mice were subjected to the intratumor and intraperitoneal injection of PBS.The size and volume of the implanted tumor were determined every week,and the growth curves of the implanted tumor after treatment were also made at the 6th week.The other four groups were therapeutic ditto,the treatment stopped after 2 weeks,and the survival time was observed.Results The growth of the implanted tumor was not significantly suppressed in group C and group C.The growth of the implanted tumor was significantly suppressed in group B,and the tumor volume in group B was smaller than in groups C and D （P ＜0.01）.The growth of the implanted tumor was suppressed more significantly in group A than in group B （P ＜ 0.01）.The average survival time in groups A,B,C and D was respectively （73.0 ± 5.6）,（54.0 ± 3.2）,（50.2 ± 3.0）,and （49.7 ± 3.7） days,and there was significant difference between group A and rest groups （P ＜ 0.01）.Conclusion SDC was effective in the AdhTERT-HSV-tk/GCV administration system and can improve the efficiency in the therapy of Human 253J carcinoma transplanted subcut
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2013年第10期2133-2135,共3页
Chinese Journal of Experimental Surgery
关键词
膀胱癌
基因治疗
重组腺病毒
端粒酶逆转录酶
Bladder carcinoma
Gene therapy
Recombinant adenovirus
Telomerase reverse
