The Effect And Mechanism Of CUDC-907 With Carfilzomib(CFZ)in Multiple Myeloma Cell Lines

Objective:1.To investigate the effection of CUDC-907 in multiple myeloma(MM)cell lines including LP-1 and U266.2.To investigate the change of cell cycle and apoptosis with the effect of Carfilzomib and CUDC-907 combination.3.To investigate the mechanism of the Carfilzomib and CUDC-907 combination about the change of cell cycle and apoptosis.To investigate the potential mechanism of the effect of Carfilzomib and CUDC-907 combination to MM cells proliferation.Methods:1.The effect of the Carfilzomib and CUDC-907 combination on the proliferation of MM cells:WST-1 assay was used to investigate the change of the cell proliferation after the Carfilzomib and CUDC-907 combination.2.The change of MM cell apoptosis after the effect of Carfilzomib and CUDC-907:Flow cytometry was used to assess the cell apoptosis change of LP-1 and RPMI 8226 after the effect of Carfilzomib and CUDC-907.3.The change of MM cell cycle after the effect of Carfilzomib and CUDC-907:Flow cytometry was used to assess the cell cycle change of LP-1、RPMI 8226 after the effect of Carfilzomib and CUDC-907.4.The mechanism of Carfilzomib and CUDC-907 combination in MM:Western blotting was used to assess the expression level of the PI3K/Akt and STAT3 signaling pathway-related protein such as Akt,p-Akt,p-STST3 et al and cell cycle,apoptosis related proteins.5.The datas were managed by SPSS 20.0.Results:1.WST-1 results:The LP-1 and U266 cell proliferation after the use of CUDC-907 were inhibited.2.Flow cytometry results:The apoptosis is apparent after the use of CUDC-907 and Carfilzomib.3.Flow cytometry results:The cell cycle arrest of LP-1 and RPMI 8226 after the use of CUDC-907 and Carfilzomib in G1 phase.4.Western Blotting results:The expression level of PI3K/Akt and STAT3 signaling pathway-related akt-p473 protein and cell cycle-related protein P21,apoptosis-related protein smac are up-regulated.Conclusion:CUDC-907 inhibit the MM cell proliferation via down-regulating the expression level of p-STAT3 protein.The use of CUDC-907 and carfilzomib in MM induce the cell apoptosis.The use of CUDC-907 and carfilzomib in MM induce the MM cell G1 phase arrest via regulating the down-regulating of cell cycle-related protein p21.