Investigating the impact of nanoparticles loaded with STAT3 and S1PR1 in cancer cells

Abstract

The expression of S1PR1, which is a G protein-coupled receptor for the lysophospholipid sphingosine-1-phosphate (S1P), is increased in STAT3-positive tumors. STAT3 is the transcription factor for the S1PR1 gene. Conversely, increased S1PR1 activates STAT3 and upregulates IL6 gene expression, thereby accelerating tumor growth and metastasis through STAT3. Shutting down S1PR1 in tumor cells or immune cells inhibits tumor STAT3 activity, tumor growth and metastasis. Materials and Methods: In this study, nanoparticles loaded with siRNA molecules were used to inhibit STAT3 and S1PR1 factors. The effect of simultaneous inhibition of the above factors on the growth and spread of cancer was performed in three mouse cancer cell lines including 4T1, CT26 and B16-F10. Results: The results of this study showed that the produced nanoparticles with appropriate physicochemical properties can significantly inhibit the expression of STAT3 and S1PR1 factors in all three cell lines. Inhibition of these two factors also reduced the expression of genes involved in cell survival, inhibited the genes that promote angiogenesis and suppressed the expression of factors involved in cell metastasis. In addition, decreased expression of STAT3 and S1PR1 induced cell death in all three cell lines.