Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice.
Adeno-associated virus-mediated doxycycline-regulatable TRAIL expression suppresses growth of human breast carcinoma in nude mice.
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DOI：
10.1186/1471-2407-12-153
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发表时间：
2012-04-24
期刊：
影响因子：
3.8
通讯作者：
Dexian Z
中科院分区：
文献类型：
--
作者：
Zheng L;Weilun Z;Minghong J;Yaxi Z;Shilian L;Yanxin L;Dexian Z
肿瘤坏死因子相关凋亡诱导配体（tumor necrosis factor-related apoptosis-inducing ligand，TRAIL）是一种细胞因子，可选择性地杀伤多种癌细胞，对大多数正常细胞无毒性。许多研究已经证明了重组可溶性TRAIL作为癌症治疗剂的潜在用途。我们已经表明，以前的管理的重组腺相关病毒（rAAV）载体表达可溶性TRAIL的结果在一个有效的抑制人肿瘤生长的裸鼠。本研究将Tet-On基因表达系统引入rAAV载体中，以控制可溶性TRAIL的表达，并评价该系统在肿瘤基因治疗中的有效性。通过荧光素酶活性测定、蛋白质印迹和酶联免疫吸附测定来确定Tet-On系统的可控性。MTT法测定细胞活力。建立乳腺癌移植瘤动物模型，通过尾静脉注射重组病毒评价其杀瘤活性。Tet-On系统可严格控制可溶性TRAIL在正常细胞和癌细胞中的表达。在诱导剂强力霉素存在下，用rAAV-TRE-TRAIL和rAAV-Tet-On转导人癌细胞系导致相当大的细胞凋亡死亡。静脉注射重组病毒可有效抑制多西环素激活的裸小鼠人乳腺癌的生长。这些数据表明，rAAV介导的可溶性TRAIL表达的Tet-On系统的控制下，是一个有前途的乳腺癌治疗策略。
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as a cytokine to selectively kill various cancer cells without toxicity to most normal cells. Numerous studies have demonstrated the potential use of recombinant soluble TRAIL as a cancer therapeutic agent. We have showed previous administration of a recombinant adeno-associated virus (rAAV) vector expressing soluble TRAIL results in an efficient suppression of human tumor growth in nude mice. In the present study, we introduced Tet-On gene expression system into the rAAV vector to control the soluble TRAIL expression and evaluate the efficiency of the system in cancer gene therapy. Controllability of the Tet-On system was determined by luciferase activity assay, and Western blotting and enzyme-linked immunoabsorbent assay. Cell viability was determined by MTT assay. The breast cancer xenograft animal model was established and recombinant virus was administrated through tail vein injection to evaluate the tumoricidal activity. The expression of soluble TRAIL could be strictly controlled by the Tet-On system in both normal and cancer cells. Transduction of human cancer cell lines with rAAV-TRE-TRAIL&rAAV-Tet-On under the presence of inducer doxycycline resulted in a considerable cell death by apoptosis. Intravenous injection of the recombinant virus efficiently suppressed the growth of human breast carcinoma in nude mice when activated by doxycycline. These data suggest that rAAV-mediated soluble TRAIL expression under the control of the Tet-On system is a promising strategy for breast cancer therapy.
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DOI：
10.2741/2354
发表时间：
2007-05-01
期刊：
FRONTIERS IN BIOSCIENCE
影响因子：
--
作者：
Schaefer, Uta;Voloshanenko, Oksana;Walczak, Henning
通讯作者：
Walczak, Henning
影响因子：
44.1
作者：
Tang, Wanhu;Wang, Weimin;Zheng, Dexian
通讯作者：
Zheng, Dexian
影响因子：
3.4
作者：
Yang, F;Shi, P;Sun, M
通讯作者：
Sun, M
影响因子：
5.4
作者：
Tang, Wanhu;Wang, Weimin;Zheng, Dexian
通讯作者：
Zheng, Dexian
影响因子：
4.8
作者：
Lee, JW;Hampl, M;Fine, HA
通讯作者：
Fine, HA