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Issue 24, 2018
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Exploring the efficacy and cellular uptake of sorafenib in colon cancer cells by Raman micro-spectroscopy

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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-RAFV600E 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-RAFV600E 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-RAFV600E or K-RASG12V 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-RAFV600E or K-RASG12V mutations. These results are in agreement with the clinical studies, where patients with the B-RAFV600E 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-RAFV600E 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.

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

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Supplementary files

Article information


Submitted
22 Oct 2018
Accepted
06 Nov 2018
First published
07 Nov 2018

Analyst, 2018,143, 6069-6078
Article type
Paper

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

H. K. Yosef, T. Frick, M. K. Hammoud, A. Maghnouj, S. Hahn, K. Gerwert and S. F. El-Mashtoly, Analyst, 2018, 143, 6069
DOI: 10.1039/C8AN02029A

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