The Effect And Mechanism Of Acetyltransferase Inhibitor In Estrogen Promoting Proliferation Of Breast Cancer Cell Line MCF-7

Objective:To investigate the effect of Garcinol inhibiting acetyltransferase on estrogen promting proliferation and transformation of cell cycle and inhibiting apoptosis of human breast cancer MCF-7cells, and to understand the effect and mechanism of changes in acetylation levels in estrogen promoting proliferation of breast cancer cells.Methods:human breast cancer MCF-7was used as the research model. The effect of Garcinol on promoting proliferation of MCF-7cells by17β-E2was investigated with CCK-8assay and the optimal concentration of Garcinol in the following experiment was determined according to the rate of inhibition. The cell cycle and apoptosis were analyzed by flow cytometry and the expression of ac-H3, ac-H4, NF-KB/ac-p65protein was determined by Western blotting analysis. The nuclear translocation of NF-KB/p65was examined by immune cell fluorescence. CyclinD1mRNA, Bcl-2mRNA, Bcl-xl mRNA expression in MCF-7cells were measured by RT-PCR and the expression of CyclinDl, Bcl-2, Bcl-xl protein was determined by Western blotting analysis.Results:With acetyltransferase inhibitor Garcinol, the proliferation of MCF-7cells treated with17β-E2was inhibited, and the transformation of MCF-7cell cycle was arrested at G0/G1phase and the rate of apoptosis increased (P<0.01); The expression level of ac-H3, ac-H4, NF-KB/ac-p65protein in MCF-7cells treated with17P-E2increased (P<0.05), which were inhibited by Garcinol but no significant effect on ac-H4(P>0.05) The nuclear translocation of NF-KB/p65in MCF-7cells treated with17β-E2was also inhibited by Garcinol (P<0.01); The promoted mRNA transcription and protein expression level of CyclinDl, Bcl-2, Bcl-xl in MCF-7cells treated with170-E2were also inhibited by Garcinol (P0.05).Conclusion:17(3-E2promting proliferation and inhibiting apoptosis of human breast cancer MCF-7cells are connected with elevated acetylation level of histone and nonhistone NF-KB/p65, acetyltransferase inhibitor Garcinol plays an inhibitive role in promoting proliferation of MCF-7by17β-E2and its important mechanism is probably associated with decreasing ac-p65protein expression level of NF-κB pathway thus down-regulating CyclinD1, Bcl-2, Bcl-xl.