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

Abstract

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.

Inhibition of GLUT-1 expression and the PI3K/Akt pathway to enhance the chemosensitivity of laryngeal carcinoma cells in vitro

“…Cisplatin is a frequently-used chemotherapeutic drug for head and neck carcinomas; it may inhibit DNA replication and harm cell membrane structures. 15 , 16 However, the development of resistance limits the clinical utility of cisplatin. 17 – 19 The expression of GLUT-1 was shown to be related to cisplatin resistance.…”

Bufalin induces DNA damage response under hypoxic condition in myeloma cells

“…Previous reports demonstrated acquisition of drug resistance by hypoxia in various types of cancer cells ( 4 , 7 – 9 , 15 ). Mechanisms regulating drug resistance under hypoxia have been described, involving microRNAs ( 16 ), the multi-drug resistant (MDR) gene ( 15 , 17 ) or the autophagy pathway ( 18 ). Modulating these pathways is thought to re-sensitize tumor cells to anti-cancer reagents.…”

AEG-1 is associated with hypoxia-induced hepatocellular carcinoma chemoresistance via regulating PI3K/AKT/HIF-1alpha/MDR-1 pathway

“…Yang et al (2016[ 28 ]) showed MDR-1 expression is up-regulated in colorectal cancer LOVO cells in CoCl₂-induced hypoxia (Yang et al, 2016[ 28 ]). In addition, MDR-1 expression in laryngeal cancer cells is increased following exposure to hypoxic environment (Li et al, 2016[ 15 ]). Herein, we observed that incubation of HCC cells in hypoxia also gave rise to up-regulation of MDR-1 in both mRNA and protein levels, thus we suggested that MDR-1 regulation mediated the actions of hypoxia-induced chemoresistance.…”