The Relationship Between The Expression Of Histone Acetyltransferase P300 And H3K56ac With Drug Resistance In Triple Negative Breast Cancer

Objective: To study the relationship between possible mechanism of drug resistance and the changes of H3K56 ac and histone acetyltransferase P300,deacetylase SIRT2 in Triple Negative Breast Cancer(TNBC).Methods: After treatment with different concentrations(0.05,0.1,0.5,1,5?g/m L)of ADR,the cell viabilities of MDA-MB-231 cell and MDA-MB-231/ADR were detected by CCK-8method and the feasible concentration was calculated.The expression levels of MDA-MB-231 cell and MDA-MB-231/ADR P300 and SIRT2 m RNA were detected by real-time fluorescent quantitative PCR and the expression levels of H3K56 ac,P300 and SIRT2 protein were detected by Western blotting.After treatment with different concentrations(5,7.5,10,25,50?g/m L)of C646 which is a kind of inhibitor of P300,the cell viabilities of MDA-MB-231 cell and MDA-MB-231/ADR were detected by CCK-8 method and the feasible concentration was calculated.The expression levels of H3K56 ac,P300 and SIRT2 protein were detected by Western blotting.Results: 1.The results of CCK-8 showed that treatment with different concentrations of ADR could inhibit the cell proliferation of MDA-MB-231 cells and MDA-MB-231/ADR increasingly(all P < 0.05).2.Compared with MDA-MB-231,the expression levels of P300 m RNA,P300 protein,SIRT2 m RNA,SIRT2 protein and H3K56 ac protein in MDA-MB-231/ADR cells were up-regulated(all P < 0.05).3.Compared with MDA-MB-231/ADR cells,the expression levels of SIRT2 m RNA in MDA-MB-231/ADR cells with treatment of ADR is down-regulated,but the expression levels of P300 and SIRT2 protein is up-regulated(all P < 0.05).4.The results of CCK-8 showed that treatment with different concentrations of ADR could inhibit the cell proliferation of MDA-MB-231 cells and MDA-MB-231/ADR cells(allP < 0.05),and the inhibition in MDA-MB-231/ADR cells is stronger than in MDA-MB-231 cells.5.Compared with MDA-MB-231/ADR cells,the expression levels of P300,SIRT2 and H3K56 ac protein in MDA-MB-231/ADR cells with treatment of C646 is down-regulated(all P < 0.05).Conclusion: In Triple Negative Breast Cancer(TNBC),up-regulated expressions of H3K56 ac mediated by histone acetyltransferase P300 and deacetylase SIRT2 maybe promotes DNA damage repair in tumor cells to build up the drug resistance.