Effect Of All Trans Retinoic Acid Combined With Suberoylanilide Hydroxamic Acid On Breast Cancer Cells MCF-7

Objective The side effects of traditional chemotherapy drugs is serious.The re search of use the small side effects of differentiation inducing agents and histone d eacetylase inhibitor for the treatment of tumors showed good application value.This study is to combine all trans-retinoic acid(ATRA)and suberoylanilide hydroxamic acid(SAHA)on the proliferation and apoptosis of MCF-7 to investigate whether the combination of the two drugs have synergistic effect.Methods Human breast can cer cell line MCF-7 was cultured in vitro.When the cells entered the logarithmic g rowth phase,a certain concentration of ATRA(B1:10?mol/L,B2:100?mol/L)(o r)SAHA(A1:4?mol/L,A2:8?mol/L)were added into the petri dishes.Morpho logical changes of cells were observed under inverted microscope,the anti-proliferat ive effect was measured by MTT assay.Flow cytometry was used to detect the ap optosis of the cells.Results Inverted microscope observation shows that,morpholo gical changes of cells in ATRA combined with SAHA group was obvious than AT RA or SAHA group,and with the extension of time the effect is more remarkable.The proliferation inhibition rate of single drug group was higher than that of the control group,and the ATRA combined with SAHA group was significantly higher than that in the single drug group(groups: F=462.792,P=0.000;different time-point:F=315.024,P=0.000;interaction: F=179.682,P=0.000);q values in A1+B1group and A2+B1group of combined effects of two drugs at 24 h and 48 h are greater than 1.15,performed as synergetic effect,q values in other groups and time points are grater than 0.85,perfomed as additive effects.Compared with the control group,the early apoptosis rate was higher in the single drug groups and combined group.But the e arly apoptosis rate of the combined group was lower than that of the single drug g roup at 24 h,and the early apoptosis rate of 48 h and 72 h in combined group w as higher than that in ATRA group but lower than SAHA group.The difference w as statistically significant(P<0.05).The rate of death and late apoptotic cells in the combination group was higher than that in the single drug groups and the control group,the difference was statistically significant(P<0.05).Conclusions ATRA and SAHA can inhibit the proliferation and promote the apoptosis of MCF-7 of breast cancer cells.ATRA combined with SAHA induced apoptosis of cells is more inte nse than the single drug groups.The combination of the two drugs has a synergistic effect.