p53AIP1增进以p53为靶点的肿瘤基因治疗效果的机制研究

p53-target tumor biological treatment strategy has great potential.At present, a representative drug of tumor gene therapy is recombinant human p53 adenovirus injection which is the first gene therapy drug in the world.It indeed brings hope for some cancer patients.How to further enhance anti-tumor effect of this drug has recently become a research focus. I have been engaged in basic research of the p53 downstream target "p53AIP1".We discovered that p53AIP1 could reversely upregulate p53 gene expression which has changed the traditional concept that p53AIP1 is p53 downstream target.This discovery will provide new opportunities for enhancing p53 target gene therapy.In our previous study on the mechanism of the p53AIP1 reversely upregulating p53 expression,we found that p53AIP1 induced upregulation of p53 protein through MDM2.But the exact mechanism is not clear and need further study.It will be significant that p53AIP1 gene could enchance the effect of p53 target gene therapy.That will make new theoretical contributions to p53 regulatory network.

以p53为靶点的肿瘤生物治疗策略，具有重要的发展潜力。国际上第一个获得正式批准的基因治疗药物- - 今又生，就是重组人p53腺病毒注射液，为广大肿瘤患者带来了希望。如何进一步提升该类药物的抗肿瘤效果，成为当前的研究热点和难点。本人长期从事p53下游促凋亡基因"p53AIP1"的基础研究，在国际上首次发现"p53AIP1"能够反向上调其上游基因p53的表达，改变了传统中已经形成的"p53AIP1是p53下游调控基因"的观念。为以p53为靶点的肿瘤基因治疗的增效，提供了新的线索和契机。我们前期初步研究了p53AIP1反向调控p53表达的相关机制发现，p53AIP1主要通过负调控MDM2的表达，来反向上调其上游基因p53的表达。但更确切的调控机制尚不明确，需要进一步深入探讨和研究。该研究对提高以p53为靶点的肿瘤基因治疗效果，将具备重要的指导意义。并为丰富p53调控网络，做出新的基础理论贡献。