RESUMO
OBJECTIVE: To compare the mechanisms of G(2)/M cycle arrest induced by topo IIalpha and IIbeta inhibitors in H460 cells. METHODS: The inhibitory effects of XK469, adriamycin and etoposide on H460 cell growth were analyzed by MTT assay. The changes in cell cycle and expressions of cdc2, phos-cdc2 and 14-3-3sigma proteins induced by these 3 topo II inhibitors were detected by flow cytometry and Western blotting, respectively. RESULTS: Both of the two types of topo II inhibitor resulted in dose-dependent G(2)/M phase arrest and growth inhibition of H460 cells, but XK469 failed to induce 14-3-3sigma protein expression as adriamycin and etoposide did. CONCLUSION: Topo IIalpha and topo IIbeta inhibitors induce growth inhibition of H460 cells possibly through two different mechanisms, namely the 14-3-3sigma-dependent pathway and the 14-3-3sigma-independent pathway, but further functional inhibition test of 14-3-3sigma is needed to confirm this hypothesis.
Assuntos
Ciclo Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/antagonistas & inibidores , Neoplasias Pulmonares/patologia , Quinoxalinas/farmacologia , Inibidores da Topoisomerase II , Antígenos de Neoplasias , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , DNA Topoisomerases Tipo II , Fase G2 , HumanosRESUMO
OBJECTIVE: To investigate the inhibitory effect of XK469 on the in vitro growth of H460 cells and its mechanism. METHODS: The survival curves of H460 cells treated with XK469, XN472 and adriamycin, respectively, were obtained by MTT analysis, and the effect of XK469 and adriamycin on the cell cycle of H460 cells examined by flow cytometry. Western blotting was adopted for detecting the expression of cdc2 and phos-cdc2 induced by XK469 and adriamycin. RESULTS: Different concentrations of XK469 and adriamycin could significantly inhibit the growth of H460 cells, induce their G2/M phase arrest, and increase phos-cdc2 expression; XN472 had a lesser effect on the growth of H460 cells. CONCLUSION: XK469 can increase phos-cdc2 expression and induce G2/M phase cell cycle arrest of H460 cells, resulting in inhibition of H460 cell growth. The inhibitory effect of XK469 on H460 cell growth is attributed to the chlorine in the 7-positon of its structure.