EFFECTS OF GAMBOGIC ACID ON THE PROLIFERATION AND CELL APOPTOSIS OF CELL LINE NCI-H929IN MULTIPLE MYELOMA

Objective To investigate the effects and its molecular mechanism of gambogic acid on cell proliferation and apoptosis multiple myeloma(MM)and provide basis for its therapy. Methods MM cell strain NCI-H929cells were treated with different concentrations of gambogic acid.The impact of gambogic acid on MM cytoactive was detected by applying MTS assay.Cell morphological changes were observed by inverted microscope and fluorescence microscope with PI staining.The changes of proteasome proteins including ubiquitin-proteasome system protein(Ubs),nuclear factorκB inhibitor protein(IκB-α),Bcl-2associated X protein(Bax),apoptosis proteins including Poly ADP-ribose polymerase(PARP),precursors of cysteinyl aspartate specific proteinase 3(Pro-caspase3),myeloid cell leukemia-1(Mcl-1),X-linked inhibitor of apoptosis protein(XIAP),B-cell lymphoma/leukemia-2(Bcl-2)and proliferation associated proteins including signal transduction and activator of transcription 5(STAT5)were tested by Western blot method. Results Gambogic acid markedly inhibited the cytoactive of NCI-H929cells and induced apoptosis.Along with the increase of gambogic acid concentration,Ubs protein accumulated,Bax expression elevated,and proteases were inhibited.Along with the increase of the gambogic acid concentration and extension of its action time,cleavage of PARP appeared, apoptosis-associated proteins Pro-caspase3,Mcl-1,XIAP,Bcl-2and the expression of proliferation-pathway-related protein STAT5 downregulated. Conclusion Gambogic acid can inhibit the proteasome activity in multiple myeloma cell line NCI-H929,impact the expression of apoptosis-related proteins and advance apoptosis.The mechanism is likely through restraining the activation of JAKs/STATs signal transduction pathway and thus inhibiting cell proliferation of this disease.