中华放射医学与防护杂志
中華放射醫學與防護雜誌
중화방사의학여방호잡지
Chinese Journal of Radiological Medicine and Protection
2009年
3期
259-264
,共6页
张敏%任军%徐博%高献书%何志嵩%何晓明%张明%刘朝兴%何新勇%曹光明%张绍龙
張敏%任軍%徐博%高獻書%何誌嵩%何曉明%張明%劉朝興%何新勇%曹光明%張紹龍
장민%임군%서박%고헌서%하지숭%하효명%장명%류조흥%하신용%조광명%장소룡
前列腺癌%基因治疗%p53腺病毒%内皮抑素%放射
前列腺癌%基因治療%p53腺病毒%內皮抑素%放射
전렬선암%기인치료%p53선병독%내피억소%방사
Prostate cancer%Genctberapy%rAd p53%Endostatin%Radiation
目的 观察放射线联合p53基因及内皮抑素治疗C57BL/6小鼠前列腺癌皮下移植瘤的效果,并初步探讨其作用机制.方法 建立C57BL/6小鼠前列腺癌皮下移植瘤模型.随机分成5组:空白组(A)、放射组(B)、放射线联合p53基因组(C)、放射线联合内皮抑素组(D)及放射线联合p53基因和内皮抑素组(E).第1天C、E组瘤内注射p53基因腺病毒(1×1010vp),第1-14天D、E组每日1次腹腔注射内皮抑素(1.5 mg/kg).第4天B、C、D、E组小鼠肿瘤区单次照射(6 MV X线DT15 Gy).每日测量肿瘤体积;检测各组肿瘤标本P53、Ki67及血管内皮生长因子(VEGF)的表达及微血管密度值(MVD).结果 4个治疗组的肿瘤生长速度均低于空白组(P=0.000),其中E组生长最慢(P<0.05).免疫组织化学结果:4个治疗组P53的表达均明显低于空白组(P=0.000);4个治疗组Ki67的表达均高于空白组,但变化趋势不同:B、C组Ki67的表达值接近,均随时间的推移而逐渐升高(P=0.000),D、E组的表达则呈现波动性;第5天时E组VEGF的表达最低(P<0.05);肿瘤生长过程中各组MVD值均持续升高,C、D、E 3组MVD值在各时间均高于空白组(P<0.05).结论 放射线联合p53基因及内皮抑素的抑瘤效果优于单独放射治疗及放射线联合p53基因或内皮抑素.三者均有自己的作用机制,但相互之间可以互相影响.
目的 觀察放射線聯閤p53基因及內皮抑素治療C57BL/6小鼠前列腺癌皮下移植瘤的效果,併初步探討其作用機製.方法 建立C57BL/6小鼠前列腺癌皮下移植瘤模型.隨機分成5組:空白組(A)、放射組(B)、放射線聯閤p53基因組(C)、放射線聯閤內皮抑素組(D)及放射線聯閤p53基因和內皮抑素組(E).第1天C、E組瘤內註射p53基因腺病毒(1×1010vp),第1-14天D、E組每日1次腹腔註射內皮抑素(1.5 mg/kg).第4天B、C、D、E組小鼠腫瘤區單次照射(6 MV X線DT15 Gy).每日測量腫瘤體積;檢測各組腫瘤標本P53、Ki67及血管內皮生長因子(VEGF)的錶達及微血管密度值(MVD).結果 4箇治療組的腫瘤生長速度均低于空白組(P=0.000),其中E組生長最慢(P<0.05).免疫組織化學結果:4箇治療組P53的錶達均明顯低于空白組(P=0.000);4箇治療組Ki67的錶達均高于空白組,但變化趨勢不同:B、C組Ki67的錶達值接近,均隨時間的推移而逐漸升高(P=0.000),D、E組的錶達則呈現波動性;第5天時E組VEGF的錶達最低(P<0.05);腫瘤生長過程中各組MVD值均持續升高,C、D、E 3組MVD值在各時間均高于空白組(P<0.05).結論 放射線聯閤p53基因及內皮抑素的抑瘤效果優于單獨放射治療及放射線聯閤p53基因或內皮抑素.三者均有自己的作用機製,但相互之間可以互相影響.
목적 관찰방사선연합p53기인급내피억소치료C57BL/6소서전렬선암피하이식류적효과,병초보탐토기작용궤제.방법 건립C57BL/6소서전렬선암피하이식류모형.수궤분성5조:공백조(A)、방사조(B)、방사선연합p53기인조(C)、방사선연합내피억소조(D)급방사선연합p53기인화내피억소조(E).제1천C、E조류내주사p53기인선병독(1×1010vp),제1-14천D、E조매일1차복강주사내피억소(1.5 mg/kg).제4천B、C、D、E조소서종류구단차조사(6 MV X선DT15 Gy).매일측량종류체적;검측각조종류표본P53、Ki67급혈관내피생장인자(VEGF)적표체급미혈관밀도치(MVD).결과 4개치료조적종류생장속도균저우공백조(P=0.000),기중E조생장최만(P<0.05).면역조직화학결과:4개치료조P53적표체균명현저우공백조(P=0.000);4개치료조Ki67적표체균고우공백조,단변화추세불동:B、C조Ki67적표체치접근,균수시간적추이이축점승고(P=0.000),D、E조적표체칙정현파동성;제5천시E조VEGF적표체최저(P<0.05);종류생장과정중각조MVD치균지속승고,C、D、E 3조MVD치재각시간균고우공백조(P<0.05).결론 방사선연합p53기인급내피억소적억류효과우우단독방사치료급방사선연합p53기인혹내피억소.삼자균유자기적작용궤제,단상호지간가이호상영향.
Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.
