Co-inhibiton of STAT3 and TIGIT factors in cancer cells by siRNA loaded nanoparticles

Abstract

A complex and extensive network of different factors in the tumor microenvironment cause the growth and proliferation of cancer cells and suppress anti-tumor immune responses. It has been shown that STAT3 and TIGIT factors play an important role in cancer progression and suppression of immune responses. On the other hand, STAT3 signaling enhances TIGIT expression. Therefore, targeting these two factors simultaneously can be considered an effective method to suppress cancer growth. On the other hand, among the various therapeutic tools, nanoparticles loaded with siRNA are known as efficient methods of cancer treatment, and these nanoparticles were used in this study. Materials and methods: In this study, trimethylchitosan alginate nanoparticles were used to transfer specific siRNA molecules against STAT3 and TIGIT molecules. Cancer cell lines 4T1 breast cancer) and B16 (melanoma) were used to study the anticancer effects of the aforementioned treatment. MTT method was used to evaluate the effect of treatment on the survival of cancer cells. Also, checking the expression of different genes was done by Real-time PCR test. Results: The appropriate physicochemical properties of nanoparticles led to the appropriate transfection of cancer cells. The entry of nanoparticles into cancer cells suppressed the expression of target genes including STAT3 and TIGIT factors. Also, suppressing the expression of these factors significantly reduced the survival of cancer cells in both cell lines. Decreased survival of cancer cells was associated with changes in the expression of molecules involved in cell apoptosis, angiogenesis, and metastasis.