Effect of nano-formulated Panitumumab on AKT/PTEN/caspase 3 apoptosis and gene expression and BAX/Bcl2 signaling pathway in KRAS-mutant SW480 cells

Background. This study aims to design and synthesize a nanostructure to address drug resistance in colorectal cancer cells. Specifically, it targets cells with mutations in the KRAS gene that resist the chemotherapy drug, Panitumumab. Then, the biological effects of this nanostructure were investigated in colorectal cancer cells (SW480). Methods. The targeted nanostructure was composed of PEGylated gold nanoparticles conjugated to Panitumumab (GNP-PEG-Pan), and its physicochemical properties were determined. The cytotoxic effects of this nanostructure on SW480 cells were assessed using the MTT assay technique. The effect of this nanostructure on apoptosis in cancer cells was evaluated using flow cytometry techniques. The expression levels of genes involved in apoptosis, including AKT, PTEN, Bax, Bcl2, and Caspase 3, were evaluated after the application of the targeted nanostructure using Real-time PCR techniques. Results. The results of the study indicated cytotoxic and apoptotic effects of the targeted nanostructure against SW480 cells and overcoming drug resistance in this cell line. This targeted nanostructure played a key role in inducing apoptosis in KRAS mutant colorectal cancer cells by increasing the expression of PTEN, Bax, and caspase 3 genes and decreasing the expression of the AKT and Bcl2 genes. Conclusion. Our findings demonstrated that the engineered nanostructure can inhibit cell proliferation and induce apoptosis in KRAS mutant colorectal cancer cells. Therefore, this nano-formulated antibody can be proposed as a novel therapeutic option for colorectal cancer and other solid tumors. Practical Implications. The engineered targeted nanostructure (GNP-PEG-Pan) enhances cytotoxic effects and induces apoptosis in KRAS-mutant CRC cells resistant to Panitumumab.