Study On Effects Of PHI On Imatinib-resistant K562/G01Cell Line And Mechanisms Of Reversal Of Drug-resistance

Objects To study PHI effected on cell growth, apoptosis and the reversal of drugresistance in K562/G01cell line in vitro.We further research the potentialmechanisms.Methods MTT assay was employed to access K562/G01cell growth inhibitionafter exposure to PHI and/or imatinib for24hours. Apoptotic rates were measured byflow cytometry with Annexin V-FITC Apoptosis Detection Kit. The proteins of Bcl-2,procaspase-3, histone acetylated H3and H4, histone methylated H3K9and H3K4,and P-gp, P210^Bcr-Abland p-P210^Bcr-Ablwere detected by Western Blot.Results PHI could inhibit the cells proliferation and induce apoptosis in K562/G01cells. The IC50s of imatinib gradually decreased with the increase of theconcentration of PHI, suggesting that PHI could partially reverse the drug-resistanceto imatinib. Apoptosis rate was higher treated by imatinib combined with PHI thanthat by imatinib or PHI alone. The study demonstrated that PHI could down regulateproteins of Bcl-2、procaspase-3and induce the accumulation of histone acetylatedH3,H4, increased histone methylation H3K4and decreased methylated H3K9. Theexpression of P210^Bcr-Abland p-P210^Bcr-Ablwas dramatically decreased after treatedwith PHI, but the alteration of P-gp was not seen.Conclusions PHI inhibited the proliferation, down regulated the expression of Bcl-2,procaspase-3and induced apoptosis in K562/G01cell line. PHI has synergistic effectwith imatinib. It partially reversed the drug-resistance to imatinib. PHI was able to upregulate the histone acetylation, modulate histone methylation, inhibited methylationon histone H3lysine9and raised methylation on H3lysine4, which were markers ofactivation of gene transcription. The mechanism of reversal of drug resistance in K562/G01cells might be by inhibiting of P210^Bcr-Abland p-P210^Bcr-Abl.