Effects of c-Kit Receptor, AKT, and NF-κB Inhibitors on Immune Evasion in Multiple Myeloma Cells

Up-regulation of immune checkpoint ligands and secretion of soluble factors in the tumor microenvironment led to the survival of cancerous plasma cells in the bone marrow milieu. Therefore, we investigate the relationship between the inhibition of c-Kit receptor, AKT, and NF-κB signaling pathways and the regulation of immune escape mechanisms in multiple myeloma. The U266B1 cell line was treated with Masitinib as a c-Kit receptor inhibitor, Perifosine as AKT inhibitor, and Bortezomib as NF-κB inhibitor either in single or combined form. Apoptosis and cell viability were evaluated using flow cytometry and MTT assays, respectively. The relative expression of programmed death-ligand 1 (PD-L1), poliovirus receptor (PVR), and interleukin 6 (IL-6) were determined by real-time PCR. Also, the secretion of IL-6 was measured by ELISA. Our findings demonstrated decreased proliferation of U266B1 cells after co-treatment with Masitinib, Perifosine, and Bortezomib. An increase in apoptosis was observed in the co-treatment of Masitinib and Perifosine. Furthermore, results elucidated that the expression of PD-L1 and IL-6 decreased after treatment with Masitinib, Perifosine, and Bortezomib in both single and co-treatments. Regarding PVR, combined treatment of U266B1 cells with Masitinib, Perifosine, and Bortezomib decreased the expression level of PVR. We showed that c-Kit receptor, AKT, and NF-κB pathway inhibitors not only serve as cytotoxic drugs but also inhibit the immune escape mechanisms of malignant plasma cells by disrupting signaling pathways.