No abstract

These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522.

AIM:To investigate the inhibitory effect of serum preparation from rabbits orally administered cobra venom (SRCV) on implanted hepatocellular carcinoma (HCC) cells in mice. METHODS:An HCC cell line, HepA, was injected into mice to prepare implanted tumors. The animals (n=30) were divided randomly into SRCV, 5-fluorouracil (5-FU), and distilled water (control) groups. From the second day after transplantation, 20 mg/kg 5-FU was administered intraperitoneally once a day for 9 days. SRCV (1 000 mg/kg) or distilled water (0.2 mL) was given by gastrogavage. Tumor growth inhibition was described by the inhibitory rate (IR). Apoptosis was detected by transmission electron microscopy (TEM), flow cytometry (FCM), and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Student's t-test was performed for statistical analysis. RESULTS:The tumor growth was inhibited markedly by SRCV treatment compared to that in the control group (P<0.01). The treatment resulted in a significant increase in the apoptotic rate of cancer cells by the factors of 10.5±2.4 % and 20.65±3.2 % as demonstrated through TUNEL and FCM assays, respectively (P<0.01). The apoptotic cells were also identified by characteristic ultrastructural features. CONCLUSION: SRCV can inhibit the growth of implantedHepA cells in mice, and the apoptosis rate appears to elevate during the process. Sun P, Ren XD, Zhang HW, Li XH, Cai SH, Ye KH, Li XK. Serum from rabbit orally administered cobra venom inhibits growth of implanted hepatocellular carcinoma cells in mice.

AIM:To compare the effect of nimesulide or/and 5-fluorouracil (5-FU) on tumor growth inhibition and apoptosis in mice with the implanted hepatoma and to observe their possible interactions. METHODS:The inhibitory effects on tumor growth was evaluated by inhibition rate. Apoptosis was assessed by the ultrastructural, flow cytometry features and the DNA ladder demonstrated by agarose gel electrophoresis. PGE 2 level was determined by radioimmunoassay. Expression levels of c-jun, c-fos and p53 were evaluated by western blotting. RESULTS:Nimesulide or 5-FU alone inhibited the growth of hepatoma, while a synergistic effect was observed for a combined use of both. More pronounced morphologic changes for tumor cell apoptosis and the DNA ladder were found for the latter treatment. Expression levels of c-jun and p53 were found to be elevated for the tumors from mice treated with nimesulide and 5-FU comparing to those with either of them, but a reduced PGE 2 level was observed only for the treatment with nimesulide. No change was detected on c-fos expression. CONCLUSION:Nimesulide and 5-FU appear to have synergistic effects for the growth inhibition and apoptosis induction. Both were found to be overexpressed in p53 and c-jun proteins, rather than that of c-fos, associations with the resulted apoptosis.

AIM:To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential ( Ψ Ψ Ψ Ψ Ψm). METHODS:Cell culture, cell counting, ELISA assay, TUNEL, flow cymetry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism.RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis.The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO. CONCLUSION:The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Ψ Ψ Ψ Ψ Ψm and JTE-522-induced apoptosis in AGS cells.