Hung Chih-Chang, Chien Chen-Yu, Chu Pei-Yu, Wu Yu-Jen, Lin Chang-Shen, Huang Chih-Jen, Chan Leong-Perng, Wang Yen-Yun, Yuan Shyng-Shiou F, Hour Tzyh-Chyuan, Chen Jeff Yi-Fu
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Head Neck. 2017 Aug;39(8):1621-1630. doi: 10.1002/hed.24803. Epub 2017 May 12.
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.
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.
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.
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.
我们之前已经表明，p22phox赋予口腔鳞状细胞癌（OSCC）对顺铂的耐药性。p22phox是否与顺铂耐药存在临床相关性以及是否影响其他铂类或非铂类药物的疗效尚不清楚。
通过免疫印迹法检测组织中p22phox的表达及细胞系中的凋亡标志物。采用甲基噻唑基四唑法测定化疗药物的细胞毒性。通过异种移植小鼠模型证实p22phox过表达肿瘤的体内化疗耐药性。
在对顺铂治疗难治的OSCC患者的肿瘤中，p22phox上调。p22phox过表达通过差异抑制药物诱导的凋亡，显著增加了OSCC细胞对顺铂和卡铂的耐药性，但对奥沙利铂和5-氟尿嘧啶（5-FU）无影响。此外，在小鼠异种移植肿瘤中证实了p22phox依赖的对顺铂而非5-FU的耐药性。
p22phox表达不仅可能是预测化疗结果的预后生物标志物，而且是口腔癌替代治疗策略的指标。
