Upregulated SLC22A3 has a potential for improving survival of patients with head and neck squamous cell carcinoma receiving cisplatin treatment

Abstract

Solute carrier family 22 member 3 (SLC22A3), also called organic cation transporter 3 (OCT3), is responsible for organic cation transport, which can eliminate many endogenous small organic cations, drugs, and toxins. This study investigated whether SLC22A3 expression is related to cisplatin uptake and the survival of patients with head and neck squamous cell carcinoma (HNSCC). Using immunohistochemical staining and digital image analysis, SLC22A3 expression was examined in 42 HNSCC patients who were postoperatively treated with or without adjuvant chemotherapy. SLC22A3-overexpressing SCC-4 cells and SLC22A3-knocked down SCC-25 cells were used to investigate the function of SLC22A3 in cisplatin uptake. We found that patients with higher SLC22A3 expression had longer survival times than those with lower SLC22A3 expression (p = 0.051). Moreover, among advanced T-stage patients receiving adjuvant cisplatin therapy, those with higher SLC22A3 expression had longer survival times than those with lower SLC22A3 expression (p = 0.006). An in vitro study demonstrated that SCC-25 cells with upregulated SLC22A3 expression were more sensitive to cisplatin than were SCC-4 cells with downregulated SLC22A3 expression. An increased uptake of cisplatin and an enhanced cytotoxic effect were observed in SLC22A3-overexpressing SCC-4 cells, and decreased uptake was found in SLC22A3-knocked down SCC-25 cells. Our results demonstrated that upregulated SLC22A3 expression can increase the cisplatin uptake and subsequently improve the survival of patients with HNSCC.