RESUMO
BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) inhibitors reportedly inhibit the growth of hepatocellular carcinoma (HCC) via caspase-dependent or caspase-independent apoptosis, which is due to COX-2 being associated with hepatocarcinogenesis. Survivin is highly expressed in most human cancers, but the mechanism regulating survivin expression remains unclear. We investigated the regulatory expression of survivin in selective-COX-2-inhibitor-induced growth inhibition of hepatoma cells. METHODS: After treatment with NS-398 (a selective COX-2 inhibitor) at various concentrations (10, 50, 100, 150, and 200 micrometer), the growth inhibition of Hep3B hepatoma cells was assessed by an MTT cell-viability assay, DNA fragmentation gel analysis, and flow cytometry. The expression of survivin transcript was analyzed by reverse-transcription polymerase chain reactions. RESULTS: NS-398 inhibited the growth of hepatoma cells by an amount dependent on the concentration and the time since treatment. Apoptotic DNA ladder and flow-cytometry shifting to the sub-G1 phase were revealed in NS-398-induced growth inhibition of hepatoma cells. NS-398 suppressed the expression of the survivin gene in a concentration- and time-dependent manner. CONCLUSIONS: Survivin was down-regulated in the growth inhibition of hepatoma cells induced by a selective COX-2 inhibitor, NS-398, in a concentration- and time-dependent manner. These results suggest the therapeutic inhibition of COX-2 via suppression of survivin in HCC.
Assuntos
Humanos , Carcinoma Hepatocelular/enzimologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/química , Fase G1 , Neoplasias Hepáticas/enzimologia , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Nitrobenzenos/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sulfonamidas/química , Fatores de TempoRESUMO
Charge transfer complexes of 3-amino-1,2,4-triazole Schiff bases with some dinitro and trinitro compounds were prepared and investigated applying IR, UV vis, 1H-NMR and ESR spectroscopy. The results revealed that complex formation takes place through pi-electron transfer only for the nonacidic or weak acidic acceptors, while with strong acidic acceptors the reaction takes place through both electron and proton transfer. The electrical properties for some CT complexes are investigated in the solid state and correlated with EA and IP. The mechanism of the conduction process in these complexes is also studied