IETD连接TRAIL和Smac的双基因溶瘤腺病毒抑制肿瘤增殖的研究

he purpose is to study the growth inhibition effect of tumor cells and the apoptosis mechanism by TRAIL and Smac dual-gene oncolytic adenovirus ZD55-TRAIL-(IETD)-Smac. The expression cassette TRAIL-(IETD)-Smac, in which the TRAIL and Smac genes were linked together by the sequence IETD, was inserted into an oncolytic adenovirus with E1B 55 kDa gene deletion (ZD55) to construct ZD55-TRAIL-(IETD)-Smac. MTT assay and crystal violet experiment suggest ZD55-TRAIL-(IETD)-Smac has an excellent antitumor effect in vitro for human hepatama, cervical, lung, nasopharyngeal and colorectal cancer cell lines but does no or little damage to normal cell lines QSG-7701 and WI38. Tumor cell apoptosis and principal protein of apoptosis pathway induced by the recombinant adenovirus were detected by Hochest33342 staining and western blot analysis, respectively. Furthermore, animal experiment showed that treatment of ZD55-TRAIL-(IETD)-Smac markedly suppressed xenograft tumor growth of nude mice bearing human lung cancer cells NCI-H460. In conclusion, the findings indicated that targeting dual gene-virus ZD55-TRAIL-(IETD)-Smac has the remarkable cancer-killing effects in vivo and in vitro and is a highly promising therapeutic agent for cancer.