Investigating the synergistic anti-cancer impact of dual blockade of STAT3 and CXCR4 in cancer cells

Abstract

inhibition of tumor promoting factors in cancer microenvironment is one of the most common methods of modern immunotherapy. Several factors are present in the tumor microenvironment, whose expression is increased and their function favors tumor growth and inhibits antitumor immune responses. The two factors STAT3 and CXCR4 are considered to be the most important players in this scenario in various cancers. Therefore, the simultaneous inhibition of these two factors can significantly help to inhibit the growth of cancer. Various methods have been used for immunotherapy. Among these methods, the use of biodegradable nanoparticles has a special place. Therefore, in this study, it was decided to use chitosan nanoparticles loaded with siRNA molecules against STAT3 and CXCR4 factors. Materials and Methods: In this study, biodegradable nanoparticles based on chitosan were used to transfer siRNA molecules against STAT3 and CXCR4 factors to two mouse cancer cell lines 4T1 (breast cancer) and B16-F10 (melanoma). After treating the cells with these nanoparticles, the survival rate of the cells was evaluated by the MTT method and the effect of the treatment on the expression of the target genes was evaluated using real-time PCR and western blot tests. Results: The results of this study showed that suppressing the expression of STAT3 and CXCR4 genes in cancer cells can decrease the survival of these cells, which was associated with an increase in the expression of genes involved in angiogenesis and metastasis and a decrease in the expression of genes that promote cell survival.