Overexpression of soluble TRAIL induces apoptosis in human lung adenocarcinoma and inhibits growth of tumor xenografts in nude mice
Overexpression of soluble TRAIL induces apoptosis in human lung adenocarcinoma and inhibits growth of tumor xenografts in nude mice
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DOI：
10.1158/0008-5472.can-04-2749
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发表时间：
2005-03-01
期刊：
影响因子：
11.2
通讯作者：
Xu, RA
中科院分区：
文献类型：
--
作者：
Shi, J;Zheng, DX;Xu, RA
重组腺相关病毒2/5（rAAV 2/5），一个杂合的rAAV-2与AAV-5衣壳，似乎是一个非常有效的肺腺癌细胞系A549的转导载体。用编码肿瘤坏死因子相关凋亡诱导配体（TRAIL，氨基酸114-281）的细胞外结构域的rAAV 2/5载体感染A549细胞系导致可溶性TRAIL（sTRAIL）的分泌和这些细胞中凋亡的诱导。rAAV 2/5-sTRAIL介导的sTRAIL递送和稳定表达导致sTRAIL的三聚体形式存在于皮下植入s.c.或原位A549肿瘤。肿瘤的rAAV 2/5-sTRAIL转导导致肿瘤生长的统计学显著减少和荷瘤动物的存活延长。原代细胞培养，肿瘤的组织学检查，和血清分析表明，在正常组织，包括肝脏中没有可检测的TRAIL诱导的毒性。成功抑制肺癌生长和没有可检测的毒性表明rAAV 2/5-sTRAIL（114-281）在肺癌治疗中的推定作用。
Recombinant adeno-associated virus 2/5 (rAAV2/5), a hybrid rAAV-2 with AAV-5 capsid, seems to be a very efficient delivery vector for the transduction of the lung adenocarcinoma cell line A549. Infection of the A549 cell line with a rAAV2/5 vector encoding the extracellular domain of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, amino acids 114-281) resulted in secretion of soluble TRAIL (sTRAIL) and induction of apoptosis in these cells. rAAV2/5-sTRAIL mediated delivery and stable expression of sTRAIL resulted in the presence of the trimeric form of sTRAIL in sera of nude mice that were implanted with s.c. or orthotopic A549 tumors. The rAAV2/5-sTRAIL transduction of the tumors resulted in a statistically significant reduction in tumor growth and prolonged survival of the tumor-bearing animals. Primary cell culture, histologic examination of the tumors, and serum analyses showed the absence of detectable TRAIL-induced toxicity in normal tissues including the liver. The successful inhibition of lung cancer growth and the absence of detectable toxicity suggest a putative role for rAAV2/5-sTRAIL(114-281) in the therapy of lung cancer.