Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain.
Oncolytic viral therapy for neuroblastoma cells with Sindbis virus AR339 strain.
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使用辛德比斯病毒 AR339 株对神经母细胞瘤细胞进行溶瘤病毒治疗。
DOI：
10.1007/s00383-015-3784-y
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Shirasawa H.
中科院分区：
文献类型：
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作者：
Takenouchi A;Saito K;Saito E;Saito T;Hishiki T;Matsunaga T;Isegawa N;Yoshida H;Ohnuma N;Shirasawa H.
目的：高危神经母细胞瘤（NB）在目前的治疗方案下，大部分仍无法治愈。溶瘤病毒疗法使用具有复制能力的病毒，如辛德毕斯病毒（SINV）来杀死癌症。SINV AR 339菌株是血液传播的，相对无毒。我们评估了SINV AR 339治疗人NB的可行性。方法SINV AR 339的细胞毒性和病毒生长进行了评估，为5个人NB细胞系，SK-N-SH，IMR-32，LAN-5，后藤，和RT-BM-1。SINV诱导的细胞凋亡通过TUNEL测定和PARP-1切割来证实。SINV对裸鼠神经母细胞瘤细胞异种移植瘤的体内影响进行了评估，通过瘤内或静脉内SINV injection.ResultsIn five human NB cell lines，SINV感染诱导显着的细胞毒性。在对SINV感染不敏感的LAN-5和RT-BM-1中，抗凋亡基因Bcl-2和Bcl-xL的mRNA表达在SINV感染后增加，而对SINV感染敏感的其他NB细胞系则无反应。在裸鼠中，瘤内和静脉注射SINV接种引起NB异种移植tumors.ConclusionOur结果表明，SINV AR 339是显着的肿瘤溶解对人类NB的显着回归。因此，SINV显示出作为治疗NB的新疗法的前景。
PurposeWith current treatment regimens, high-risk neuroblastoma (NB) remains largely incurable. Oncolytic viral therapy uses replication-competent viruses, likeSindbis virus(SINV), to kill cancers. The SINV AR339 strain is blood borne and relatively non-virulent. We evaluated the feasibility of SINV AR339 for treating human NB.MethodsThe cytotoxicity and viral growth of SINV AR339 were evaluated for five human NB cell lines, SK-N-SH, IMR-32, LAN-5, GOTO, and RT-BM-1. SINV-induced apoptosis was confirmed by TUNEL assays and PARP-1 cleavage. In vivo effects of SINV on neuroblastoma cell xenografts in nude mice were assessed by intratumoral or intravenous SINV inoculation.ResultsIn five human NB cell lines, SINV infections induced remarkable cytotoxicity. The mRNA expressions of anti-apoptotic genes, Bcl-2 and Bcl-xL, in LAN-5 and RT-BM-1, which were less sensitive to SINV infection, increased in response to SINV infection, while the other NB cell lines sensitive to SINV infection failed to respond. In nude mice, intratumoral and intravenous SINV inoculations caused significant regression of NB xenograft tumors.ConclusionOur results suggested that SINV AR339 was significantly oncolytic against human NB. Thus, SINV showed promise as a novel therapy for treating NB.