Evaluation of the effect of combined inhibition of CD73 and ꞵ-catenin molecules in inhibiting the growth of cancer cells

Abstract

Immunotherapy has been one of the most attractive methods of cancer treatment in the last two decades. Tumor microenvironment management has been able to bring many hopes for cancer treatment. Important molecules increased in cancer microenvironment include CD73 and ꞵ-catenin. The increased expression of these two molecules in the tumor area causes the growth and spread of cancer cells. On the other hand, these molecules can help cancer progress faster by inhibiting the immune system and facilitating angiogenesis and metastasis. Therefore, inhibiting these two factors can significantly suppress tumor growth and induce anti-tumor immune responses. In this regard, suppressing the expression of the aforementioned genes using chitosan-based biodegradable nanoparticles loaded with siRNA molecules can be considered one of the useful methods for cancer treatment. Materials and Methods: In this study, chitosan-based nanoparticles were used to transfer specific siRNA molecules against CD73 and ꞵ-catenin to the cells of three cancer cell lines including 4T1, CT26 and B16-F10. The effect of treatment on cell survival was evaluated using MTT test. Also, the study of the effect of treatment expression on the expression of target genes was investigated using Real-time PCR test. Results: The results of the study showed that the treatment of cells with nanoparticles loaded with siRNA significantly suppressed the expression of CD73 and ꞵ-catenin factors in all three cell lines. Suppressing the expression of these factors led to a decrease in the survival of cancer cells. Also, combined treatment led to a decrease in the expression of genes involved in cell survival, angiogenesis, and metastasis.