Enhancement of cisplatin on cytocidal effect of tineposide against small cell lung cancer cell line / 基础医学与临床

ABSTRACT

Objective To investigate the mechanism of cisplatin enhanceing the effect of tineposide killing small cell lung cancer cell line by combination of the two drug.Methods The microculture tetrazolium(MTT) assay was used to determine the inhibition rates of CDDP combined with VM-26.Acridine orange/ethidium bromide(AO/EB) fluorescent staining was used to show the cell vitality rates,DNA disruption ladder were applied to reveal cell apoptosis.The mRNA and protein level of topoisomerase Ⅱ(Topo Ⅱ) and transcript factor SP1 were measured by semi-quantitative RT-PCR and western blot.Results There is synergistic effect between the two drug.The cell vitality rates were decreased in combination group than that of CDDP or VM-26 used alone.the combination treatment group resulted in more serious DNA strand breakage.The expression of Topo Ⅱ?,? and SP1 mRNA and protein both increased in CDDP treatment group,while the Topo Ⅱ?,? expression decreased and(the SP1 expression) has no obviously change in VM-26 treatment group.In combination group,Topo Ⅱ? expressionwere decreased comparing with CDDP used alone,SP1 expression increased comparing with VM-26 used alone,but has no obviously change as comparing with CDDP used alone.Conclusion CDDP could enhance Topo Ⅱ expression through up-regulating SP1 expression,which offer more target for Topo Ⅱ inhibitor VM-26 to act on killing small cell lung cancer cell.