[Effect of G Protein-coupled Receptor Kinase 6 on Proliferation and Apoptosis of Multiple Myeloma Cells and Its Mechanisms].

OBJECTIVE

To study the effect of G protein-coupled receptor kinase 6(GRK6) on proliferation and apoptosis of multiple myeloma(MM) cells and its mechanisms.

METHODS

The samples were collected from MM patients and healthy people for study in vivo. The plasma cells isolated from multiple myeloma patients, as well as U266 and NCI H929 myeloma cell lines were used for study in vitro. Western blot and quantitative real-time PCR were used to evaluate the protein and mRNA of expression of GRK6 in multiple myeloma, cell proliferation and apoptosis were tested by BrdU and Annexin V-FITC/PI assays.

RESULTS

The protein and mRNA expression of GRK6 in multiple myeloma was higher than those in control group, and the expression level of GRK6 in stage I of MM was higher than that in control group, while the expression level of GRK6 in stage II was higher than that in stage I, but lower than that in stage III (P<0.05). U266 and MM cells showed high-sensitivity to CX-4945, except NCI H929. GRK6 expression level in U266, NCI H929 and MM cells treated with siRNA and CX-4945, significantly decreased as compared with those cells treated by CX-4945 alone. Cell proliferations of U266, NCI H92 and MM groups treated with CX-4945 were (58.25±18.24)%, (64.32±20.03)% and (45.42±25.01)% respectively, moreover, their apoptotic rates were (62.82±53.21)%, (43.25±47.05)% and (85.67±40.32)% respectively.

CONCLUSION

The expression level of GRK6 in multiple myeloma increases, and GRK6 inhibitor CX-4945 inhibits proliferation and promotes apoptosis of myeloma cells; GRK6 regulates Rac1 and involves in the proliferation and apoptosis pathway of multiple myeloma cells.