Abstract
Cisplatin is among the most widely used anticancer drugs used in the treatment of several malignancies, including oral cancer. However, cisplatin treatment often promotes chemical resistance, subsequently causing treatment failure. Several studies have shown that epidermal growth factor receptors (EGFRs) play a variety of roles in cancer progression and overcoming cisplatin resistance. Therefore, this study focused on EGFR inhibitors used in novel targeted therapies as a method to overcome this resistance. We herein aimed to determine whether the combined effects of cisplatin and cetuximab could enhance cisplatin sensitivity by inhibiting the epithelial-to-mesenchymal transition (EMT) process in cisplatin-resistant cells. In vitro analyses of three cisplatin-resistant oral squamous cell carcinoma cells, which included cell proliferation assay, combination index calculation, cell cytotoxicity assay, live/dead cell count assay, Western blot assay, propidium iodide staining assay, scratch assay, and qRT-PCR assay were then conducted. Our results showed that a cisplatin/cetuximab combination treatment inhibited cell proliferation, cell motility, and N-cadherin protein expression but induced E-cadherin and claudin-1 protein expression. Although the combination of cisplatin and cetuximab did not induce apoptosis of cisplatin-resistant cells, it may be useful in treating oral cancer patients with cisplatin resistance given that it controls cell motility and EMT-related proteins.
Highlights
Cisplatin treatment dose-dependently inhibited cell growth in YD-9/CIS and YD-38/CIS (Figure 1a), only a slight suppression was observed in YD-8/CIS
A DNA-damaging agent, is a well-known anticancer drug widely used in the chemotherapy of various human cancers, including oral cancers [9,26,27]
Patients receiving cisplatin-based treatments often exhibit lower response rates during subsequent treatment [28,29]. This problem can be attributed to several reasons, with some studies suggesting the importance of epithelial-tomesenchymal transition (EMT) in the development of resistance to cisplatin treatment [28,29,30,31]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Studies have shown that the overexpression of the epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, was associated with the development of various cancers [1,2,3]. Evidence has found that the activation of the EGFR signaling pathway promotes the proliferation, invasion, and metastasis of cancer cells [4,5,6]. The diverse roles of the EGFR in cancer progression have facilitated the development of anticancer therapies that interfere with EGFR-mediated effects, such as monoclonal antibodies and small-molecule tyrosine kinase inhibitors [4,7,8]
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