Role of caspase-8 and DR5 in TRAIL-induced apoptosis of neuroblastoma cells.
- Author:
Hai-Xia TONG
1
;
Ji-Hong ZHANG
;
Li MA
;
Chun-Wei LU
;
Jin-Hua ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; Apoptosis Regulatory Proteins; pharmacology; Blotting, Western; Caspase 8; Caspases; physiology; Humans; Interferon-gamma; pharmacology; Membrane Glycoproteins; pharmacology; Neuroblastoma; pathology; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor; physiology; TNF-Related Apoptosis-Inducing Ligand; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; pharmacology; Tumor Suppressor Protein p53; physiology
- From: Chinese Journal of Contemporary Pediatrics 2006;8(4):327-330
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETumor necrosis factor related apoptosis inducing ligand (TRAIL) induces cell death in a variety of tumors but not in normal cells. TRAILdouble ended arrow-resistance of most neuroblastoma (NB) cell lines is related to the loss of caspase-8 expression and the expression and distribution of membrane TRAIL-receptors. This study investigated the role of caspase-8 and DR5 in TRAIL-induced apoptosis of NB cell line SKNDZ.
METHODSThe expression of caspase-8 mRNA was detected by RT-PCR. The expression of DR5 protein was detected by Western Blot analysis. The effects of TRAIL, IFNgamma +TRAIL, chemotherapeutic agent (adriamycin or etoposide) + TRAIL, and chemotherapeutic agent +TRAIL+ IFNgamma on the growth and apoptosis of SKNDZ cells were detected by MTT assay and flow cytometry.
RESULTScaspase-8 was not expressed in SKNDZ cells but IFNgamma treatment resulted in an increase of caspase-8 expression. Expression of DR5 protein was not detected in SKNDZ cells but an increased DR5 protein expression was found after treatment with adriamycin or etoposide. The SKNDZ cells expressing caspase-8 were not sensitive to TRAIL but those SKNDZ cells expressing both caspase-8 and DR5 were sensitive. The early apoptosis rates of the adriamycin /etoposide + IFNgamma+TRAIL groups [(17.9 +/- 3.6)%, (14.8 +/- 3.3)%] were higher than that of the IFNgamma+TRAIL group [(3.9 +/- 1.2)% ](F=26.233, P < 0.01).
CONCLUSIONSSKNDZ cells expressing both caspase-8 and DR5 restored the TRAIL sensitivity. Caspase-8 and DR5 play a key role in TRAIL-induced apoptosis of NB cells.
