Eur J Pediatr Surg 2011; 21(5): 304-309
DOI: 10.1055/s-0031-1279762
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

Combination of IFNγ and Chemotherapeutic Agents Increase TRAIL Sensitivity of Neuroblastoma Cell Lines

H. X. Tong1 , C. W. Lu2 , Q. S.  Wang1 , L. Y. Ma1
  • 1Shengjing Hospital of China Medical University, Department of Blood Transfusion, Shenyang, China
  • 2College of Public Health, China Medical University, Section of Health Testing, Shenyang, China
Further Information

Publication History

received January 25, 2011

accepted after revision April 21, 2011

Publication Date:
12 July 2011 (online)


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.



Prof. Tong Haixia

Shengjing Hospital of

China Medical University

Department of Blood


NO. 39 Huaxiang Road

Tiexi District

110022 Shenyang