论文部分内容阅读
目的:观察人端粒酶逆转录酶(hTERT)启动子驱动辣根过氧化物酶(HRP)/吲哚乙酸(IAA)系统联合白细胞介素-12(IL-12)基因对小鼠Lewis肺癌的疗效。方法:建立Lewis肺癌移植瘤模型,随机分为对照组、HRP组、IL-12组和联合组,分别给予AdCMVGFP、AdhTERTHRP、AdCMVmIL-12单一或联合注射,然后腹腔注射IAA,观察肿瘤生长情况。蛋白质印迹法和ELISA检测瘤组织HRP和IL-12表达;免疫组化检测瘤组织内CD4+、CD8+淋巴细胞浸润情况。结果:与对照组、单一治疗组相比,联合组小鼠肿瘤生长受到显著抑制(联合组vs对照组:P=0.000,9 d;联合组vsHRP组:P=0.005,15 d;联合组vsIL-12组:P=0.046,12 d),生存期显著延长(联合组vs对照组:χ2=9.529,P=0.002;联合组vsHRP组:χ2=9.039,P=0.003;联合组vsIL-12组:χ2=8.595,P=0.003),肿瘤组织广泛坏死,CD4+、CD8+淋巴细胞浸润显著增多。结论:IL-12基因治疗可诱导宿主产生抗肿瘤免疫应答,与靶向HRP/IAA自杀基因系统联合具有协同抗肿瘤作用。
OBJECTIVE: To observe the effect of human telomerase reverse transcriptase (hTERT) promoter-driven HRP / IAA combined with interleukin-12 (IL-12) Efficacy. Methods: Lewis lung cancer xenografts model was established and randomly divided into control group, HRP group, IL-12 group and combination group. AdCMVGFP, AdhTERTHRP and AdCMVmIL-12 were injected singly or in combination. Then IAA was injected intraperitoneally to observe tumor growth. Western blotting and ELISA were used to detect the expression of HRP and IL-12 in tumor tissue. The infiltration of CD4 + and CD8 + lymphocytes in tumor tissues was detected by immunohistochemistry. Results: Compared with the control group and the monotherapy group, the tumor growth of the combination group was significantly inhibited (combination group vs control group: P = 0.000,9 d; combination group vs HRP group: P = 0.005,15 d; combination group vsIL -12 group: P = 0.046,12 d), the survival time was significantly prolonged (combined group vs control group: χ2 = 9.529, P = 0.002; combined group vs HRP group: χ2 = 9.039, P = 0.003; : χ2 = 8.595, P = 0.003), extensive tumor necrosis, CD4 +, CD8 + lymphocyte infiltration significantly increased. Conclusion: IL-12 gene therapy can induce the host to produce antitumor immune response, which has synergistic anti-tumor effect with targeting HRP / IAA suicide gene system.