Investigation of the effect of nanoparticeles loaded with the siRNA molecules against P68 and STAT3 in the growth inhibition and development of cancer cells

Abstract

Since several factors are involved in the tumorigenesis process, targeting only one factor most probably cannot overwhelm cancer progression. Therefore, it seems that combination therapy through targeting more than one cancer-related factor may lead to cancer control. The expression and function of P68, involved in several cellular processes, is dysregulated in various cancers. P68 is also a co-activator of many oncogenic transcription factors such as the STAT3, which contributes to cancer progression. This close connection between p68 and STAT3 plays an important role in the growth and development of cancer. So, we used siRNA loaded chitosan NPs for synchronous inhibited the P68/STAT3 axis in cancer cells. Materials and Methods: In this study, we applied for PEG-TMC-HA NPs for purposeful transfer siRNA to suppress the p68 / STAT3 axis. Conjugation of HA can enhance cellular uptake of NPs through binding to CD44 molecules overexpressed on cancer cells. After suppressing the expression of target genes, the effect of their inhibition on different behaviors of cancer cells such as proliferation, survival, apoptosis, angiogenesis and metastasis was evaluated.Results: siRNA-loaded NPs notably suppressed the expression of p68/STAT3 axis in cancer cells, which was associated with blockade of tumor growth, colony formation, angiogenesis, and cancer cell migration. In addition to apoptosis induction, this combined therapy also reduced the expression of several tumor-promoting factors including FGF, VEGF, TGF-β, MMP-2, MMP-9, HIF-1α, IL-6, IL-33, Bcl-x, vimentin and snail.