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SRC3 plays critical roles in various biological processes of diseases,including proliferation,apoptosis,migration,and cell cycle arrest.However,the effect of SRC3 expression in mesenchymal stem cells (MSCs) on multiple myeloma (MM) is not clear yet.In our study,MSCs (MSC-SRC3,MSC-SRC3-/-) and MM cells were co-cultured in a direct or indirect way.The proliferation of MM cells was studied by CCK-8 and colony formation assays.The apoptosis and cell cycle of MM cells were detected by flow cytometry.In addition,the expressions of proteins in MM cells were detected by weste blot analysis and the secretions of cytokines were measured by ELISA.Our data showed that the expression of SRC3 in bone marrow mesenchymal stem cells (BM-MSCs) could promote cell proliferation and colony formation of MM cells through accelerating the transformation of the G1/S phase,no matter what kind of culture method was adopted.Meanwhile,SRC3 expressed in BM-MSCs could inhibit the apoptosis of MM cells through the caspase apoptosis pathway and mitochondrial apoptosis pathway.Moreover,SRC3 could enhance the adhesion ability of MM cells through up-regulating the expression of adhesion molecules including CXCL4,ICAM1,VLA4,and syndecan-1.SRC3 also played a regulatory role in the progress of MM through the NF-KB and PI-3K/Akt pathways.SRC3 expressed in MSCs was found to promote the growth and survival of MM cells,while SRC3 silencing in MSCs could inhibit the development of MM.These results would be useful for developing a more effective new strategy for MM treatment.