Synergistic effect of suberoylanilide hydroxamic acid and tumor necrosis factor-related apoptosis-inducing ligand on proliferation of triple-negative breast cancer cell line MDA-MB-231 cells

ObjectiveTo explore the synergistic effect of suberoylanilide hydroxamic acid (SAHA) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on proliferation of triple-negative breast cancer MDA-MB-231 cells.MethodsHuman breast cancer MDA-MB-231 cells were treated with SAHA,TRAIL,and SAHA+TRAIL,except for the cells of the control group.Viability,apoptosis and cell cycle of the MDA-MB-231 cells were detected with Muse Cell Analyzer.The mRNA and protein levels of related apoptotic factors in MDA-MB-231 cells were determined with real-time PCR and solid phase apoptosis antibody microarray.ResultsCompared with that of the control group (96.6%),the cell viability of MDA-MB-231 cells of SAHA,TRAIL,and SAHA+TRAIL groups were 82.5%,87.1%,and 57.6%,respectively,and were significantly lower.In addition,the results suggested a synergistically inhibitive effect of combined SAHA and TRAIL treatment on the viability of MDA-MB-231 cells;the live ratio was decreased by 39% and the proportion of alive cells was reduced by more than 40% for the MDA-MB-231 cells with combined treatment of SAHA and TRAIL.Real-time PCR and apoptosis antibody array results showed that the combined treatment of SAHA and TRAIL enhanced the activity of caspase-3,TRAIL DR5,and p21^CIP1 and reduced the expressions of Bcl-2,Bcl-x,and p53 in breast cancer cells.Furthermore,combined treatment of SAHA and TRAIL activated the cell death pathway related with TRAIL,thereby inducing the apoptosis of MDA-MB-231 cells.ConclusionCombined treatment of SAHA and TRAIL has a synergistically inhibitive effect on proliferation of triple-negative breast cancer MDA-MB-231 cells;the mechanism of the effect may be correlated to the activation of TRAIL related apoptotic pathways and the induction of cell apoptosis.