Effect of shikonin on multiple myeloma cells by regulating the cAMP/PKA/CREB signaling pathway
Objective To investigate the effect of shikonin on cyclic adenosine monophosphate(cAMP)/protein kinase(PK)A/cAMP response element binding protein(CREB)signaling pathway on multiple myeloma cells.Methods The logarithmically grown RPMI-8226 cells were divided into A(blank)group,B(250 μmol/L shikonin)group,C(500 μmol/L shikonin)group,D(1 000 μmol/L)shikonin group,E(SQ22536)group and F(1 000 μmol/L shikonin+SQ22536)group.The apoptosis was observed by Hoechst 33324 staining and flow cytometry.Cell counting kit(CCK)-8 was used to detect cell proliferation.The level of cAMP was detected by enzyme linked immunosorbent assay(ELISA).The expression levels of pathway-related proteins,cyclin D1 and cleaved caspase-3 were detected by western blot.Results Compared with group A,the proliferation rate and cyclin D1 expression of RPMI-8226 cells in group E were significantly increased,and the apoptosis rate,cAMP level,cleaved caspase-3,p-PKA/PKA,and p-CREB/CREB expressions were significantly decreased(P＜0.05).However,cell proliferation rate and cyclin D1 expression were significantly decreased in groups B,C and D,and apoptosis rate,cAMP level,cleaved caspase-3,p-PKA/PKA,and p-CREB/CREB expression were significantly increased,with statistical differences among different concentrations(P＜0.05).Compared with group E,cell proliferation rate and cyclin D1 expression in group F were significantly decreased,apoptosis rate,cAMP level,cleaved caspase-3,p-PKA/PKA,and p-CREB/CREB expression were significantly increased in group F(P＜0.05).Compared with group D,cell proliferation rate and cyclin D1 expression in group F were significantly increased,apoptosis rate,cAMP level,cleaved caspase-3,p-PKA/PKA,and p-CREB/CREB expression were significantly decreased(P＜0.05).Conclusion Shikonin inhibits the cell proliferation and promote apoptosis of MM cells by regulating the cAMP/PKA/CREB signaling pathway.
shikonincyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate response element binding protein signaling pathwaymultiple myelomaproliferationapoptosis
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