Combinatorial inhibition of CD73 and EP4 RECEPTOR in order to suppression the cancer cells growth

Abstract

Tumor microenvironment is one of the main causes of failure of many cancer immunotherapy methods. Immunosuppressive molecules in the tumor microenvironment inhibit anti-tumor immune responses and accelerate the growth of tumor cells. One of the most important axes of tumor growth is the CD73 / EP4 axis. The CD73 molecule becomes adenosine, which is an inhibitor of the immune system. The EP4 molecule is also one of the receptors that plays an important role in tumor growth and development. As a result, targeting these two molecules simultaneously can be an effective treatment for cancer. Materials and Methods: In this study, superparamagnetic iron oxide (SPION) nanoparticles were used to suppress the expression of CD73 and EP-4 molecules. The effectiveness of combination therapy was determined on three cancer cell lines including 4T1, CT26 and B16-F10. Results: The results showed that the synthesized nanoparticles had a size of about 133 nm, with a dispersion coefficient of less than 0.3 and a zeta potential of about 25. Suitable physicochemical properties of the nanoparticles gave them a good potential for siRNA delivery. Also, siRNA-loaded nanoparticles significantly inhibited the expression of CD73 and EP4 molecules in cancer cells. Inhibition of these molecules suppressed proliferation, colonization, migration, and angiogenesis in cancer cells.