title: Effect of multidrug resistance 1/P-glycoprotein on the hypoxia-induced multidrug resistance of human laryngeal cancer cells.
abstract: 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.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Affiliated Eye and Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Affiliated Eye and Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.
authors.forename: Jiameng
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Affiliated Eye and Ear, Nose and Throat Hospital of Fudan University, Shanghai 200031, P.R. China.
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xiao
keywords: P-glycoprotein; cell hypoxia; laryngeal neoplasms; multiple drug resistance