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

Abbas Ranjbar; Saeid Taghiloo; Parvin Nozari; Akbar  Hedayatizadeh-Omran; Hossein  Asgarian-Omran

doi:10.18502/ijaai.v24i1.18024

Abbas Ranjbar Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Saeid Taghiloo Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Parvin Nozari Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Akbar Hedayatizadeh-Omran Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
Hossein Asgarian-Omran Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

DOI: https://doi.org/10.18502/ijaai.v24i1.18024

Keywords: Immune evasion; Immune checkpoint; Multiple myeloma; Signaling pathways; Small molecule inhibitor

Abstract

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.