CAJ | 학술논문

目的观察真核表达载体Ad-hTRAIL转染124膀胱癌组织的效果及其联合丝裂霉素C(MMC)对膀胱肿瘤的治疗作用.方法采用皮下肿块移植法制作荷T24膀胱癌BALB/C-nu小鼠模型40只,随机分成4组,分别腹腔注射MMC(A组),瘤内注射Ad-hTRAIL(B组),联合注射MMC+Ad-hTRAIL(C组),对照给予PBS+Ad空载体(D组).给药结束2周后,测量小鼠体重,所荷肿瘤的直径和重量,用逆转录-聚合酶链反应(RT-PCR)和Western blot测量肿瘤组织内hTRAIL mRNA及TRAIL蛋白的表达水平.结果 4组小鼠给药前体重及所荷肿瘤平均直径差异无统计学意义(P>0.05);给药结束2周后,A、B、C组所荷肿瘤直径和重量均显著小于D组(P<0.01),而C组又显著小于A、B组(P<0.01),B组又显著小于A组(P<0.01);A、C组体重均显著小于D组(P<0.01),而B组和D组差异无统计学意义(P>0.05);B、C组肿瘤组织内均有hTRAIL mRNA和TRAIL蛋白的表达,且两组间表达相对量差异无统计学意义(P>0.05),而A、D组则无hTRAIL mRNA和TRAIL蛋白的表达.结论在体内实验研究中,Ad-TRAIL能成功转染T24膀胱癌组织且表达TRAIL蛋白;MMC和Ad-hTRAIL对T24膀胱癌有明显的抑制作用,且两者联用具有协同作用.
목적 관찰진핵표체재체Ad-hTRAIL전염124방광암조직적효과급기연합사렬매소C(MMC)대방광종류적치료작용.방법 채용피하종괴이식법제작하T24방광암BALB/C-nu소서모형40지,수궤분성4조,분별복강주사MMC(A조),류내주사Ad-hTRAIL(B조),연합주사MMC+Ad-hTRAIL(C조),대조급여PBS+Ad공재체(D조).급약결속2주후,측량소서체중,소하종류적직경화중량,용역전록-취합매련반응(RT-PCR)화Western blot측량종류조직내hTRAIL mRNA급TRAIL단백적표체수평.결과 4조소서급약전체중급소하종류평균직경차이무통계학의의(P>0.05);급약결속2주후,A、B、C조소하종류직경화중량균현저소우D조(P<0.01),이C조우현저소우A、B조(P<0.01),B조우현저소우A조(P<0.01);A、C조체중균현저소우D조(P<0.01),이B조화D조차이무통계학의의(P>0.05);B、C조종류조직내균유hTRAIL mRNA화TRAIL단백적표체,차량조간표체상대량차이무통계학의의(P>0.05),이A、D조칙무hTRAIL mRNA화TRAIL단백적표체.결론 재체내실험연구중,Ad-TRAIL능성공전염T24방광암조직차표체TRAIL단백;MMC화Ad-hTRAIL대T24방광암유명현적억제작용,차량자련용구유협동작용.
Objective To study the therapeutic effects of eukaryotic expression vector coding hu-man tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) combined with mitomycin C (MMC) on bladder carcinoma in vivo. Methods Forty BALB/c-nu mice bearing T24 bladder carcinoma were obtained by tumor transplantation and divided into 4 groups : Group A were intraperitoneally injected with mitomycin C, group B intratumorally injected with Ad-hTRAIL, group C injected with MMC + Ad-Htrail and group D with PBS + nude Ad-vector (control group). Two weeks after the injection, the body weights of the mice and the diameters and weights of their bearing tumors were measured. RT-PCR and Western blot were applied to detect the levels of hTRAIL mRNA and TRAIL protein in the bearing tumors.Results Before the injecton,there were no significant differences in mice body weights and tumor diame-ters among the the 4 groups (P > 0.05). Two weeks after the injection, the tumor diameters and weights in groups A, B and C were significantly decreased as compared with those in group D (P < 0.01), and those in group C were significantly decreased as compared with those in groups A and B (P <0.01) ,and those in group B were significantly decreased as compared with those in group A (P < 0.01). The body weights in groups A and C were significantly decreased as compared with those in group D (P <0.01), but there was no significant difference between groups B and D (P > 0.05). There was obvious expression of hTRAIL mRNA and TRAIL protein in the tumors of groups B and C, and there were no significant differ-ences in relative expressing amounts of the mRNA and protein between the two groups (P > 0.05). There was no positive expresion of hTRAIL mRNA and TRAIL protein in the tumors of groups A and D. Conclu-sion The Ad-TRAIL can be transfected into the T24 bladder tumors and TRAIL protein can be expressed successfully in vivo. MMC and Ad-hTRAIL play significant anti-tumor effects on T24 bladder carcinoma, and combined use of them exerts synergistic effects.