The ubiquitin-proteasome pathway plays a critical role in the degradation of cellular proteins and cell cycle control. Dysregulating the degradation of such proteins should have profound effects on @entity5 growth and causes cells to undergo apoptosis. The aims of this study are to evaluate the ubiquitin-proteasome pathway in @entity356 and the potential role of pharmacological inhibition of proteasome on induction of apoptosis in @entity356 cells. @entity356 cell lines @entity15206 ( @entity876 wild-type) and MKN-28 ( @entity876 mutant) were treated with proteasome inhibitor @entity16626 . The results showed that @entity16626 inhibited cell proliferation in @entity15206 and MKN-28 cells in a time- and dose-dependent manner. The inhibition of cell proliferation was caused by apoptosis which was also time- and dose-dependent. @entity15206 cells were more responsive to @entity16626 than MKN-28 cells. Induction of apoptosis was preceded by the activation of @entity522 , as measured by a colorimetric @entity522 cellular activity and Western blotting of the cleavage of @entity522 and its substrate @entity12982 . Activation of @entity14544 was also exhibited. In addition, z-VAD-fmk, a broad spectrum caspase inhibitor, reversed apoptosis induced by @entity16626 in @entity15206 and MKN28 cells. Although z-DEVD-fmk, a specific @entity522 inhibitor, suppressed @entity16626 -induced apoptosis in MKN28 cells, it only partially rescued the apoptotic effect in @entity15206 cells. @entity522 activation was the result of release of @entity4674 from mitochondria into the cytosol, as a consequence of upregulation of bax. There were overexpressions of all the proteasome-related proteins @entity876 , @entity994 ( @entity994 ) and @entity5438 ( @entity13525 ) at 4 hr after proteasome inhibition which was identified by the accumulation of ubiquitin-tagged proteins. This was accompanied by accumulation of cells at G(1) phase. Our present study suggests that inhibition of proteasome function in @entity356 cells induces apoptosis and proteasomal inhibitors have potential use as novel anticancer drugs in @entity356 .

Inhibition of proteasome function induced apoptosis in XXXX .

@entity522 :: ('836', 'Gene') :: ['caspase-3', 'Caspase-3'] @entity5438 :: ('3429', 'Gene') :: ['p27'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity4674 :: ('54205', 'Gene') :: ['cytochrome c'] @entity16626 :: ('MESH:C072553', 'Chemical') :: ['MG132'] @entity14544 :: ('840', 'Gene') :: ['caspase-7'] @entity12982 :: ('142', 'Gene') :: ['PARP'] @entity876 :: ('7157', 'Gene') :: ['p53'] @entity13525 :: ('1027', 'Gene') :: ['kip1'] @entity15206 :: ('MESH:C535607', 'Disease') :: ['AGS'] @entity356 :: ('MESH:D013274', 'Disease') :: ['gastric cancer', 'Gastric cancer'] @entity994 :: ('1026', 'Gene') :: ['waf1', 'p21']
@entity356 :: (MESH:D013274,Disease) :: ['gastric cancer']
