CAJ | 학술논문

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.
목적 관찰Scopadulciol(SDC)재인단립매역전록매(hTERT)계동자조공선병독개도적단순포진병독흉선격매기인/병양조감(HSV-tk/GCV)자살기인계통대라서방광암적체내살상작용중적증효작용.방법 수선건립인방광암라서피하이식류모형,당종류생장지직경약위6mm혹체적위100 mm3시,수궤분위4조,매조4지.A조위Ad-hTERT-HSV/tk+ GCV+ SDC조:우제1、5、10천매지라서종류내주사Ad-hTERT-HSV/tk(1×109 pfu)0.1 ml,제2천개시복강주사GCV(2.0 mg/d)×15 d화SDC(1 mg/d)×15 d.B조위Ad-hTERT-HSV/tk+ GCV조:주사Ad-hTERT-HSV/tk、GCV동A조.C조위Ad-hTERT-HSV/tk+ SDC조:주사Ad-hTERT-HSV/tk、SDC동A조.D조위대조조:라서종류내급복강내부주사린산염완충액(PBS).자주사약물개시,매7d용원규화유표잡척측량종류대소,계산종류적체적,묘회종류적생장곡선,공관찰6주.령작4조치료동상,2주후정지치료,기록각조라서적존활기,이관찰대조조화치료조존활기적개변.결과 단순Ad-hTERT-tk/SDC(C조)급대조조(D조)대종류생장무억제혹촉진작용；이경과Ad-hTERT-tk/GCV치료적B조라서,현시출대종류유억제작용,기체적저우C、D조(P＜0.01),Ad-hTERT-HSV/tk/GCV+ SDC치료적A조억제종류작용경위명현,비교B조유명현적증강작용,여B조비교차이유통계학의의(P＜0.01),여C、D량조비교차이유통계학의의(P＜0.01).B、C、D각조하류라서적평균존활기분별위(54.0±3.2)、(50.2±3.0)화(49.7±3.7)d,이A조하류라서평균존활기연장지(73.0±5.6)d,여기여각조조비교차이유통계학의의(P＜0.01).결론 Scopadulciol대흉선격매의뢰적GCV조단방광암진전유일정적증효작용,장Scopadulciol여아문구건적구유종류특이성적중조선병독Ad-hTERT-HSV-tk이급GCV연합응용우인방광암라서피하이식류모형적치료,구유명현증효작용.
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 subcutaneously in nude mice.