Increasing the sensitivity of chronic lymphocytic leukemia cells to apoptosis by Doxorubicin and BCL-2-siRNA to reduce BCL-2 gene expression

Abstract

These days, nanoparticles are considered one of the most important drug carriers, including chitosan-based nanoparticles, which are widely studied because of their ideal gene therapeutic properties. In this study, in order to transfer siRNA, trimethyl chitosan coated with carboxymethyl dextran was synthesized. Cancer treatment is for those who have tried to cure cancer by inducing apoptosis. One of the main causes of this resistance is the high expression of IAP in these cells, which inhibits caspases. STAT3 as a multifunctional agent is an important factor in tumor cell growth and survival and its inhibition can induce effective apoptosis in tumor cells. Therefore, STAT3 inhibitors were used in this study to induce apoptosis and BV6 to prevent apoptotic resistance. Methods In this study, the ion gelation method was used to synthesize the nanoparticles, then the nanoparticle formation and physicochemical properties of the nanoparticles were investigated using SEM, hNMR and FTIR methods. BV6 and siRNA were then used against STAT and NIK to prevent the possible effect of BV6 on induction of apoptosis. These factors were used independently and in combination. To evaluate the toxicity of the MTT assay, the gene expression of Realtime PCR, the cell migration of the scratch test, the angiogenesis assay of the CAM assay, and the colony formation assay were used. Results This study has two main stages as follows. In the first step, we designed a chitosan nanoparticle called TMC-CMD which, due to its physico-chemical properties, increases the rate of drug delivery and thus improves the therapeutic effect of siRNAs. Thus, NP-TMC-CMD carries a non-viral efficacy for gene therapy. Secondly, combination therapy includes anti-STAT3 siRNA with BV6 highly effective therapy for inhibiting apoptosis, preventing apoptotic resistance, inhibiting angiogenesis, metastasis and cell migration in breast, colon and melanoma cancers. Inhibition of different pathways seems to have promising results compared to inhibition of a signaling pathway. Combining this with nanoparticles can be a promising way to treat tumors We also first received IC50 for BV6 for murine tumor cells, which may be useful in future studies and in the use of BV6 in breast, colon and murine melanoma.