AK-968 Efficiently Inhibits Proliferation And Induces Cell Apoptosis In Human Multiple Myeloma Cells

Background:Multiple myeloma(MM)is a plasma cell malignancy originated from B cell.Malignant plasma cell(myeloma cell)proliferation and accumulation in bone marrow results in increased level of monoclonal immune globulin in the blood and urine,bone destruction,decreased normal immunoglobulins,renal insufficiency and so on.In recent years,some new treatment options have been widely used,such as proteasome inhibitors or immunomodulatory drugs and hematopoietic stem cell transplantation(SCT)after high-dose chemotherapy.Currently,the commonly used chemotherapy protocols for MM include lenalidomide plus low-dose dexamethasone regimens,bortezomib containing regimens,carfilzomib-lenalidomide-dexamethasone regimens,etc.These regimens combined with SCT have significantly improved treatment outcomes in terms of progress free survival(PFS)and overall survival(OS)of multiple myeloma patients.However,MM eventually relapse after a few year-remission.Therefore MM remains an incurable malignant disease and developing new therapeutic drugs are urgently required.Objective:In recent years,the treatment of multiple myeloma has made significant progress,but the mortality rate and recurrence rate of patients are still high.The five-year survival rate of patients with multiple myeloma is about 49%.The development of new drugs and the combination of new drugs and traditional drugs have been a hot issue in the research field of multiple myeloma.In the current study,we eva'luated potential anti-MM activity of the small molecular weight compound AK-968.Our results showed that AK-968 effectively inhibited the proliferation of myeloma cells and induced myeloma cell apoptosis.Materials and methods:1.Synthesis of small molecular weight compound AK-9682.in vitro culture of human multiple myeloma cell lines3.Flow cytometry technique applied to quantify cell apoptosis and analyze mitochondrial membrane potential4.MTT used to evaluate myeloma cell proliferation5.West blot used to determine apoptosis mechanisms6.Statistical AnalysisResults and conclusions:1.AK-968 inhibited the growth of human myeloma cell lines.2.AK-968 induced apoptosis of human myeloma cell lines.3.Ak-968 promotes apoptosis by activating caspase-3.4.AK-968 affected the mitochondrial membrane potential of apoptotic cells.AK-968 significantly inhibited myeloma cell proliferation and induced myeloma cell apoptosis through induction of mitochondrial membrane integrity damage and caspase activation.