%0 Journal Article
%T Enhanced antitumor effect of combining interferon β with TRAIL mediated by tumor-targeting adeno-associated virus vector on A549 lung cancer xenograft
肿瘤靶向腺相关病毒携带干扰素β和TRAIL对A549肺癌移植瘤的增强治疗效应
%A Yigang Wang
%A Lingfeng He
%A Guoqing He
%A Yanping Kong
%A Xuping Liu
%A Haibo Cai
%A Xinyuan Liu
%A Wensong Tan
%A
王毅刚
%A 何凌峰
%A 何国清
%A 孔彦平
%A 刘旭平
%A 蔡海波
%A 刘新垣
%A 谭文松
%J 生物工程学报
%D 2010
%I
%X Interferon β (IFN-β) and TNF-related apoptosis-inducing ligand (TRAIL) are effective anticancer agents.Adeno-associated virus (AAV) is one of the current most promising gene delivery vectors. Previously, we constructed tumor-targeting AAV-hTERT-IFN-β and AAV-hTERT-TRAIL by inserting IFN-β or TRAIL gene into AAV controlled by hTERT promoter. The studies showed that either single IFN-β or TRAIL gene therapy exhibited a certain extent anticancer effect. Here,we report their inhibitory effects on A549 lung cancer cell growth in vitro and in vivo by combined AAV-hTERT-IFN-β and AAV-hTERT-TRAIL. Expression of secreted IFN-β in lung cancer A549 cells infected by AAV-hTERT-IFN-β was detected by enzyme-linked immunosorbent assay (ELISA). The growth-suppressing effect of AAV-hTERT-IFN-β in combination with AAV-hTERT-TRAIL on several cancer cell lines was assessed by MTT assay. Apoptosis of A549 cancer cells infected by AAV-hTERT-IFN-β alone, AAV-hTERT-TRAIL alone, and their combination was evaluated by apoptotic cell staining and flow cytometry (FCM), respectively. The antitumor effect of the combination of AAV-hTERT-IFN-β with AAV-hTERT-TRAIL in vivo was further evaluated through A549 lung cancer xenograft in nude mice. The results showed that the combinational treatment was superior to any alone and presented intensified tumor cytotoxic and apoptotic effect on A549 cancer cells. Most importantly, the combination of AAV-hTERT-IFN-β with AAV-hTERT-TRAIL exhibited significant antitumor effect and eliminated all tumor masses in nude mice, which lay a foundation for exploring the molecular mechanisms of combined IFN-β and TRAIL anti-tumor activity.
%K IFN-β
%K TRAIL
%K adeno-associated virus
%K lung cancer
%K antitumor effect
干扰素β,TRAIL,腺相关病毒,肺癌,抗肿瘤效应
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=90BA3D13E7F3BC869AC96FB3DA594E3FE34FBF7B8BC0E591&jid=A66E90C274451689E69F6F0291467824&aid=7CC884F25D2E1AE31F1148695550E501&yid=140ECF96957D60B2&vid=96C778EE049EE47D&iid=B31275AF3241DB2D&sid=5E191A234CD3698F&eid=E339BF74025BB291&journal_id=1000-3061&journal_name=生物工程学报&referenced_num=1&reference_num=0