Exploring the efficacy and cellular uptake of sorafenib in colon cancer cells by Raman micro-spectroscopy

Abstract

In recent years, many subcellular proteins have emerged as promising therapeutic targets in oncology. One crucial target is the epidermal growth factor receptor. Inhibition of this receptor has significantly improved the survival rate of patients for many cancers. However, oncogenic mutations such as B-RAF^V600E have rendered tumours resistant to this therapeutic approach. Therefore, this mutation has emerged as a potential target for cancer therapy. Sorafenib is developed to overcome the B-RAF^V600E mutation and restore the response of the mutated tumour to therapy. Here, we explore the efficacy and distribution of sorafenib at a cellular level using colon cancer cell lines with B-RAF^V600E or K-RAS^G12V mutations. The Raman results detected significant sorafenib-induced spectral differences in both cell lines. In addition, the western blot and real-time cell analysis in vitro assays revealed that the ERK phosphorylation and the cellular proliferation of cells are inhibited, respectively, in the sorafenib-treated cells. Thus, the observed Raman spectral changes illustrate the potent effect of sorafenib on cells despite the presence of the B-RAF^V600E or K-RAS^G12V mutations. These results are in agreement with the clinical studies, where patients with the B-RAF^V600E mutation respond to sorafenib. Furthermore, the Raman spectral imaging results have shown the uptake and the distribution of sorafenib in colon cancer cells with the B-RAF^V600E mutation through its label-free marker bands in the fingerprint region. The present results of sorafenib efficacy and distribution in cells demonstrate the potential of Raman micro-spectroscopy as the in vitro assay for the assessment of drugs, which is important in drug discovery.