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)

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.

References

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