Differential susceptibility of metastatic and primary oral cancer cells to TRAIL-induced apoptosis.

摘要: TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) preferentially induces apoptosis of cancer cells without toxicity in normal cells. plays an important role host immune surveillance against tumor metastasis. Cathepsin B (CB) is a mediator whose activity regulated by its inhibitors, known as cystatins. We examined the TRAIL-mediated cytotoxicity rates clonally-related primary and metastatic oral (OC) correlated them with expression levels receptors, cathepsin cystatins A, B, C M. Two pairs (686Tu 101A) (686Ln 101B) OC cell lines were treated various concentrations (5 to 1000 ng/ml) recombinant human protein for 14 h, viability apoptotic rate determined. In both lines, revealed greater susceptibility than their counterparts. The synthesis inhibitor cycloheximide markedly increased sensitivity these whereas CB-specific chemical CA-074 reduced TRAIL. DNA laddering M30 CytoDEATH immunodetection assays confirmed that TRAIL-induced death process. Expression (DR4 DR5) decoy (DcR1 DcR2) receptors not different between However, higher respective cells, CB remain unchanged. Elevated may cause resistance apoptosis. Our data suggest high confer phenotype enhancing