重组腺病毒p53基因治疗肝癌研究进展

目的：探讨重组腺病毒p53基因（recombinant humanAd—p53，rAd—p53）治疗肝癌的抗肿瘤机制及临床应用。方法：应用PubMed、万方和CNKI数据库，以“肝癌、重组腺病毒p53基因、基因治疗、实验研究和临床应用”为关键词，检索1994—06—01—2013—11—31文献739篇，纳入标准：1）p53基因与肝癌发生的相关性；2）重组腺病毒p53基因抗肿瘤机制；3）重组腺病毒p53治疗肝癌的实验研究；4）重组腺病毒p53治疗肝癌的临床应用研究。根据纳入标准选择符合分析的文献36篇。结果：p53基因是公认的肿瘤抑制基因，具有促使肿瘤细胞自杀和帮助缺陷细胞修复的作用。rAd—p53是复制缺陷型5型腺病毒载体与人p53基因重组的肿瘤基因治疗制品。rAd-p53通过多种途径发挥抗肿瘤作用，包括使肿瘤的细胞周期阻滞和发生程序性死亡，促进放射线对肿瘤细胞引起的细胞周期阻滞和凋亡，刺激机体产生抗肿瘤免疫反应，抑制肿瘤血管内皮生长因子，控制肿瘤的血管生成，使注射部位瘤组织产生局部血供障碍和坏死。此外，还能增加肝癌细胞的放化疗敏感性，间接增强抗肿瘤疗效。rAd-p53基因疗法为肝癌治疗开辟了崭新的途径，多项-l盘床研究疗效良好。结论：rAd—p53基因对肿瘤的作用机制体现了在抗肿瘤治疗方面的有效性，并在基础研究及临床应用中均取得了显著进展，再肝癌的防治中将取得更大的突破。

Advance in using recombinant human adenovirus p53 preparation for treatment of primary hepatocellular carcinoma

OBJECTIVE.. To explore the antitumor mechanism and clinical application of recombinant adenovirus p53 gene （Gendicine,rAd-p53） on liver cancer patients. METHODS： PubMed, wanfang database, CNKI were searched using ＂hepatocellular, adenovirus p53 gene, Gene therapy, experimental study, Clinical application＂ as key words from 1994-06-01 to 2013-11-31,739 references were obtained and the inclusion criteria were as follows： 1） the relationship be- tween p53 gene and the liver cancer; 2）the antitumor mechanism of rAd-p53; 3）the experimental research of rAd-p53; 4） clinical application of rAd-p53. According to inclusion criteria a total of 36 articles were analyzed. RESULTS.. p53 gene is a recognized tumor suppressor genes,it promps tumor cell suicide and repairs the defect cell repaired, rAd-p53 is gene therapy product recombined from defected type 5 adenovirus vector and p53 gene. Its antitumor effect is through various channels such as inducing apoptosis and arresting tumor cell cycles. It can increase the tumor cell cycle arrest and apoptosis caused by radiotherapy and stimulate antitumor immune responses, inhibit tumor vascular endothelial growth factor and tumor angiogenesis. Direct injection into tumor tissue produces local blood supply obstacles and necrosis. In addition,it al- so can increase the radiational and chemotherapeutic sensitivity of liver cancer cells,indirectly enhance antitumor efficacy. Many clinical studies confirmed the curative effect of tAd-p53. CONCLUSIONS： rAd-p53 is effective in anti-tumor treat- ment. Many basic and clinical researchs support the application of rAp-p53 in the prevention and treatment of liver cancer.