Effect of multidrug resistance 1/P-glycoprotein on the hypoxia-induced multidrug resistance of human laryngeal cancer cells

被引:28
作者
Li, Dawei [1 ]
Zhou, Liang [2 ]
Huang, Jiameng [2 ]
Xiao, Xiyan [2 ]
机构
[1] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Otolaryngol Head & Neck Surg, 600 Yishan Rd, Shanghai 200233, Peoples R China
[2] Eudan Univ, Affiliated Eye & Ear Nose & Throat Hosp, Dept Otolaryngol Head & Neck Surg, Shanghai 200031, Peoples R China
基金
中国博士后科学基金;
关键词
cell hypoxia; P-glycoprotein; multiple drug resistance; laryngeal neoplasms; INDUCIBLE FACTOR-1-ALPHA; P-GLYCOPROTEIN; CARCINOMA TISSUE; GENE-EXPRESSION; LUNG-CANCER; MDR1; GENE; FACTOR-I; CHEMOTHERAPY; TRANSPORTER; CISPLATIN;
D O I
10.3892/ol.2016.4749
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In a previous study, it was demonstrated that hypoxia upregulated the multidrug resistance (MDR) of laryngeal cancer cells to chemotherapeutic drugs, with multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp) expression also being upregulated. The present study aimed to investigate the role and mechanism of MDR1/P-gp on hypoxia-induced MDR in human laryngeal carcinoma cells. The sensitivity of laryngeal cancer cells to multiple drugs and cisplatin-induced apoptosis was determined by CCK-8 assay and Annexin-V/propidium iodide staining analysis, respectively. The accumulation of rhodamine 123 (Rh123) in the cells served as an estimate of drug accumulation and was evaluated by flow cytometry (FCM). MDR1/P-gp expression was inhibited using interference RNA, and the expression of the MDR1 gene was analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting. As a result, the sensitivity to multiple chemotherapeutic agents and the apoptosis rate of the hypoxic laryngeal carcinoma cells increased following a decrease in MDR1/P-gp expression (P<0.05). Additionally, FCM analysis of fluorescence intensity indicated that the downregulated expression of MDR1/P-gp markedly increased intracellular Rh123 accumulation (P<0.05). Such results suggest that MDR1/P-gp serves an important role in regulating hypoxia-induced MDR in human laryngeal carcinoma cells through a decrease in intracellular drug accumulation.
引用
收藏
页码:1569 / 1574
页数:6
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