Enhanced effect of IFNgamma on the induced apoptosis of neuroblastoma cells by cytotoxic drugs.
The objective of this study was to explore the antitumor effects of cytotoxic drugs combined with IFNgamma on neuroblastoma cell line SH-SY5Y cells. The expression of caspase 8 mRNA and protein was detected with RT-PCR and Western blot analysis. The effects of cytotoxic drugs and IFNgamma combined with cytotoxic drugs on the growth and apoptosis of SH-SY5Y cells were detected with the methods of MTT and flow cytometry. Caspase 8 activity was measured by colorimetric assay. Caspase 8 was undetectable in SH-SY5Y cells with an increased expression of caspase 8 after the treatment of IFNgamma. SH-SY5Y cells were sensitive to Adriamycin relatively but resistant to TNFalpha and TRAIL, while IFNgamma-pretreated SH-SY5Y cells were more sensitive to the cytotoxic drugs with an increase of caspase 8 activity. The authors conclude that IFNgamma can sensitize SH-SY5Y cells to Adriamycin-, TNFalpha-, and TRAIL-induced apoptosis and this may be realized by the upregulation of caspase 8.
Tong
Hai-xia
HX
Laboratory of Hematology, Shengjing Hospital of China Medical University, Shenyang, China. tonghaixia18@yahoo.com.cn
Lu
Chun-wei
CW
Zhang
Ji-hong
JH
Zhang
Jin-hua
JH
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009447:Neuroblastoma / Q000188:drug therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D003603:Cytotoxins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D007371:Interferon-gamma; C505530:CASP8 protein, human; D053181:Caspase 8