Upregulated SLC22A3 has a potential for improving survival of patients with head and neck squamous cell carcinoma receiving cisplatin treatment
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Cheng-Ming Hsu1,2,3, Pai-Mei Lin4, Jan-Gowth Chang5,6,7, Hsin-Ching Lin2, Shau-Hsuan Li8, Sheng-Fung Lin9,10 and Ming-Yu Yang2,3
1Department of Otolaryngology, Chiayi Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Chiayi, Taiwan
2Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
3Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan
4Department of Nursing, I-Shou University, Kaohsiung, Taiwan
5Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan
6College of Medicine, China Medical University, Taichung, Taiwan
7Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan
8Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
9Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
10Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Ming-Yu Yang, email: [email protected]
Sheng-Fung Lin, email: [email protected]
Keywords: SLC22A3, cancer therapy, cisplatin, survival, head and neck squamous cell carcinoma
Received: June 16, 2017 Accepted: August 17, 2017 Published: September 04, 2017
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.
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