Investigating the impact of concomitant silencing of CD73 and IGF-1 in cancer cells

Abstract

New methods of immunotherapy by targeting factors in the tumor microenvironment have kept many hopes alive for cancer treatment. The increased expression of adenosine in the tumor microenvironment is caused by the increased expression of adenosine production facilitating factors such as CD73. The central involvement of IGF signaling in tumor cell proliferation, survival, invasion and metastasis has made it an attractive therapeutic target. Therefore, blocking the function of CD73 and IGF-1 using siRNA molecules leads to inhibition of tumor cell growth. Materials and methods: This study was conducted on two mouse cancer cell lines including 4T1 (mouse breast cancer) and CT26 (mouse colon cancer). In this study, the effect of chitosan-based nanoparticles loaded with anti-CD73 and IGF-1 siRNA molecules was evaluated. The effect of treatment on cell survival was evaluated using the MTT method and the effect of treatment on the expression of target genes was evaluated using the Real-time PCR method. Results: The results of this research showed that chitosan nanoparticles could transfer siRNA molecules to cancer cells with high efficiency and suppress the expression of CD73 and IGF-1 factors in both cell lines. Also, combined treatment reduced the survival of cancer cells. In addition, exposure of cells to nanoparticles loaded with siRNA had an effect on the expression of genes involved in apoptosis, angiogenesis, metastasis and cell proliferation.