Chih-Chang Hung1,2, Chen-Yu Chien3,4,5, Pei-Yu Chu6, Yu-Jen Wu7, Chang-Shen Lin1, Chih-Jen Huang8, Leong-Perng Chan4, Yen-Yun Wang9,10, Shyng-Shiou F Yuan9,10,1,11, Tzyh-Chyuan Hour12, Jeff Yi-Fu Chen2. 1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 2. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan. 3. Department of Otorhinolaryngology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 4. Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 5. Department of Otorhinolaryngology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 6. Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan. 7. Department of Biological Science and Technology, Meiho University, Pingtung, Taiwan. 8. Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 9. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 10. Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 11. Department of Obstetrics and Gynecology and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 12. Institute of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract
BACKGROUND: We have previously shown that p22phox confers resistance to cisplatin in oral squamous cell carcinoma (OSCC). Whether p22phox has clinical correlation with cisplatin resistance and affects the efficacy of other platinum or nonplatinum drugs is unknown. METHODS: The p22phox expression in tissues and apoptotic markers in cell lines was detected by immunoblotting. The cytotoxicity of chemotherapy drugs was determined by methylthiazol tetrazolium assay. In vivo chemoresistance of p22phox-overexpressing tumors was confirmed by the xenograft mouse model. RESULTS: The p22phox was upregulated in tumors of patients with OSCC refractory to cisplatin treatment. The p22phox overexpression markedly increased the resistance to cisplatin and carboplatin, but not oxaliplatin and 5-fluorouracil (5-FU), in OSCC cells by differentially inhibiting the drug-induced apoptosis. Furthermore, p22phox-dependent resistance to cisplatin, but not 5-FU, was demonstrated in mouse xenograft tumors. CONCLUSION: The p22phox expression may not only be a prognostic biomarker for prediction of chemotherapy outcomes, but the indication for alternative treatment strategies in oral cancer.
BACKGROUND: We have previously shown that p22phox confers resistance to cisplatin in oral squamous cell carcinoma (OSCC). Whether p22phox has clinical correlation with cisplatin resistance and affects the efficacy of other platinum or nonplatinum drugs is unknown. METHODS: The p22phox expression in tissues and apoptotic markers in cell lines was detected by immunoblotting. The cytotoxicity of chemotherapy drugs was determined by methylthiazol tetrazolium assay. In vivo chemoresistance of p22phox-overexpressing tumors was confirmed by the xenograft mouse model. RESULTS: The p22phox was upregulated in tumors of patients with OSCC refractory to cisplatin treatment. The p22phox overexpression markedly increased the resistance to cisplatin and carboplatin, but not oxaliplatin and 5-fluorouracil (5-FU), in OSCC cells by differentially inhibiting the drug-induced apoptosis. Furthermore, p22phox-dependent resistance to cisplatin, but not 5-FU, was demonstrated in mousexenograft tumors. CONCLUSION: The p22phox expression may not only be a prognostic biomarker for prediction of chemotherapy outcomes, but the indication for alternative treatment strategies in oral cancer.