Decorin gene upregulation mediated by an adeno-associated virus vector increases intratumoral uptake of nab-paclitaxel in neuroblastoma via inhibition of stabilin-1
The availability of effective medication for the treatment of refractory or recurrent neuroblastoma remains limited. This study sought to investigate the effects of increased decorin (DCN) expression on the intratumoral uptake of nab-paclitaxel as a potential novel approach to NB. Correlation between the clinical characteristics of neuroblastoma and the expression of DCN, secreted protein acidic and rich in cysteine (SPARC) and stabilin-1 was evaluated. The anticancer effect of recombinant adeno-associated virus-DCN (rAAV-DCN) was assessed in vivo and in vitro. And the effect of rAAV-DCN on the intratumoral uptake of paclitaxel was also studied in neuroblastoma-grafted nude mice. Overall, 12.5%, 17.7%, and 71.9% of the tumors stained positive for DCN, SPARC and stabilin-1 respectively and correlated to age, stage and N-MYC status in 96 children and adolescents with neuroblastoma. Transfected neuroblastoma cells stably expressed DCN, with in vivo and in vitro studies demonstrating rAAV-DCN sensitized the anticancer effect of nab-paclitaxel. Systemic rAAV-DCN in neuroblastoma-grafted nude mice inhibited stabilin-1, up-regulated SPARC, and increased the intratumoral uptake of paclitaxel. Macrophage depletion or anti-stabilin-1 monoclonal antibody increased the intratumoral uptake of nab-paclitaxel and its anticancer effects to a degree comparable to that achieved by systemic rAAV-DCN. The systemic administration of rAAV-DCN up-regulates DCN in neuroblastoma and accelerates the intratumoral uptake of nab-paclitaxel by inhibiting stabilin-1 mediated SPARC degradation.
基金：
Science and Technology Planning Project of Guangdong Province, China [2012B031800460, 2013B021800069]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|3 区医学
小类|2 区药学3 区肿瘤学
最新[2023]版：
大类|3 区医学
小类|3 区药学4 区肿瘤学
第一作者：
第一作者机构：[1]State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China;[2]Sun Yat Sen Univ, Dept Pediat Oncol, Ctr Canc, 651 Dongfeng Rd East, Guangzhou 510060, Guangdong, Peoples R China;[3]Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China;
通讯作者：
通讯机构：[1]State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China;[2]Sun Yat Sen Univ, Dept Pediat Oncol, Ctr Canc, 651 Dongfeng Rd East, Guangzhou 510060, Guangdong, Peoples R China;[3]Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China;
推荐引用方式(GB/T 7714)：
Zhen Zijun,Yang Kaibin,Ye Litong,et al.Decorin gene upregulation mediated by an adeno-associated virus vector increases intratumoral uptake of nab-paclitaxel in neuroblastoma via inhibition of stabilin-1[J].INVESTIGATIONAL NEW DRUGS.2017,35(5):566-575.doi:10.1007/s10637-017-0477-5.
APA：
Zhen, Zijun,Yang, Kaibin,Ye, Litong,You, Zhiyao,Chen, Rirong&Liu, Ying.(2017).Decorin gene upregulation mediated by an adeno-associated virus vector increases intratumoral uptake of nab-paclitaxel in neuroblastoma via inhibition of stabilin-1.INVESTIGATIONAL NEW DRUGS,35,(5)
MLA：
Zhen, Zijun,et al."Decorin gene upregulation mediated by an adeno-associated virus vector increases intratumoral uptake of nab-paclitaxel in neuroblastoma via inhibition of stabilin-1".INVESTIGATIONAL NEW DRUGS 35..5(2017):566-575
