Evaluation of the effect of combination therapy of cancer cells using suppression of IL-6 and inhibition of CDKs

Abstract

In recent years, the use of new drug delivery methods has found a special place in cancer immunotherapy-based treatments. Targeted delivery of specific anticancer drugs using nanocarriers has been evaluated in various studies. In this study, the delivery of the drug Dinacicilib, which can efficiently inhibit the activity of CDK kinases, in combination with anti-IL-6 siRNA in cancer cells has been investigated. CDK kinases play an important role in the proliferation and survival of cancer cells. On the other hand, cytokine IL-6 also plays a very vital role in the proliferation, survival, angiogenesis, and metastasis of cancer cells. Therefore, the targeted and combined inhibition of these two factors in cancer cells can be considered a useful method in cancer treatment. Materials and methods: In this study, we used lactated chitosan nanoparticles that were targeted with folic acid. These nanocarriers were used for targeted delivery of Dinacicilib and anti-IL-6 siRNA to cancer cells. Studies were conducted on 4T1 cell line, which is derived from mouse breast cancer. The effect of treatment on cell survival was determined using the MTT method. Real-time PCR and ELISA methods were also used to evaluate the effect of treatment on the expression of target genes. Findings: The results of this study showed that the produced nanocores could transfer treatments to cancer cells with high efficiency and induce cell death in them. Also, combined treatment had a significant effect on the expression of genes involved in apoptosis, angiogenesis, and cell metastasis.