Identification of differentially expressed proteins in tumour necrosis factor-alpha-resistant and -sensitive rat hepatoma cells.

BACKGROUND

Our earlier studies reported that ONO-4007, a synthetic lipid A analogue with low endotoxic activity, had shown much effect on tumour necrosis factor (TNF)-alpha-sensitive rat hepatoma cells, even though it had no effect on TNF-alpha-resistant cells.

METHODS

To find biomarkers which relate to the sensitivity of cancer cells to TNF-alpha, proteomic differential display analysis for TNF-alpha-resistant cKDH-8/11 and -sensitive KDH-8/YK rat hepatoma cell lines was carried out using two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry.

RESULTS

Two-DE analysis showed 32 spots, whose expression was different between cKDH-8/11 cells and KDH-8/YK cells. Of these, 12 were up-regulated and 20 were down-regulated in cKDH-8/11 cells compared to KDH-8/YK cells. The up-regulated proteins include transitional endoplasmic reticulum ATPase, 78 kDa glucose-regulated protein (GRP78), heat-shock cognate 71 kDa protein (HSC71) and protein disulfide-isomerase A6. The down-regulated proteins included alpha-enolase, aldose reductase, glutathione reductase, annexin A1, glutamate dehydrogenase 1 and dihydrolipoyl dehydrogenase.

CONCLUSIONS

These findings suggest that these differentially regulated proteins could be factors responsible for the resistance of cKDH-8/11 cells to TNF-alpha-induced cell death.