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DOI: 10.1055/s-0031-1279762
© Georg Thieme Verlag KG Stuttgart · New York
Combination of IFNγ and Chemotherapeutic Agents Increase TRAIL Sensitivity of Neuroblastoma Cell Lines
Publication History
received January 25, 2011
accepted after revision April 21, 2011
Publication Date:
12 July 2011 (online)
![](https://www.thieme-connect.de/media/ejps/201105/lookinside/thumbnails/10.1055-s-0031-1279762-1.jpg)
Abstract
Objective: Aim of the study was to further evaluate the role of caspase 8 and death receptors (DR) in the TRAIL-induced apoptosis of neuroblastoma (NB) cell lines.
Methods: Caspase 8 mRNA expression was monitored by RT-PCR. Caspase 8, DR5 and DR4 protein expression were monitored by Western blot analysis. The effects of IFNγ, TRAIL, IFNγ+TRAIL, caspase 8 inhibitor+TRAIL and IFNγ+chemotherapeutic agents+TRAIL on the growth and apoptosis of NB cells were detected with MTT and flow cytometry. The relative caspase 8 activity was measured with colorimetric assay.
Results: Caspase 8 expression was induced by IFNγ in the NB cell line SKNDZ. TRAIL alone did not induce apoptosis compared with controls but a combination of IFNγ+TRAIL and IFNγ+chemotherapeutic agents+TRAIL significantly induced cell apoptosis in SY5Y cells. Etoposide and doxorubicin induced DR5 but not DR4 in NB cell lines. SKNDZ cells expressing caspase 8 after treatment with IFNγ were still resistant to TRAIL but sensitive to TRAIL after the induction of DR5.
Conclusions: Sensitization of NB cells to TRAIL may be mediated by the upregulation of caspase 8 with IFNγ and DR5 with chemotherapeutic agents. This suggests that caspase 8 and death receptors play a very important role in TRAIL-induced apoptosis of NB cells and a combination of IFNγ, TRAIL and chemotherapeutic agents may be a new and interesting anticancer treatment strategy for NB.
Key words
neuroblastoma - caspase 8 - TRAIL - death receptor
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Correspondence
Prof. Tong Haixia
Shengjing Hospital of
China Medical University
Department of Blood
Transfusion
NO. 39 Huaxiang Road
Tiexi District
110022 Shenyang
China
Email: tonghx2009@163.com