MEK inhibitor enhances sensitivity to chemotherapeutic drugs in multidrug resistant hepatocellular carcinoma cells

Meng,Qingliang; He,Xiaoqi; Xie,Guangwei; Tian,Qingzhong; Shu,Xiaogang; Li,Jin; Xiao,Yong

doi:10.3892/ol.2017.6494

MEK inhibitor enhances sensitivity to chemotherapeutic drugs in multidrug resistant hepatocellular carcinoma cells

Authors:
- Qingliang Meng
- Xiaoqi He
- Guangwei Xie
- Qingzhong Tian
- Xiaogang Shu
- Jin Li
- Yong Xiao
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Affiliations: Department of Oncological Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, P.R. China, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: June 30, 2017 https://doi.org/10.3892/ol.2017.6494
Pages: 3089-3095

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Abstract

The aim of the present study was to investigate the association between the mitogen‑activated protein kinase (MAPK) signal transduction pathway and multidrug resistance in hepatocellular carcinoma cells. A Cell Counting Kit‑8 assay was used to determine the drug sensitivity of HepG2 and HepG2/ADM hepatocellular carcinoma cell lines in combination with the MAPK/extracellular‑signal‑regulated kinase kinase (MEK) inhibitor U0126. Flow cytometry was used to analyze the rate of apoptosis. The reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to determine P‑glycoprotein (P‑gp) and multidrug resistance‑associated protein 1 (MRP1) mRNA expression following treatment with various concentrations of U0126. P‑gp and MRP1 expression levels were measured using Western blot analysis. The half‑maximal inhibitory concentration was markedly decreased in combination with U0126. RT‑qPCR results demonstrated that the expression of multidrug resistance 1 (MDR1) and MRP1 in HepG2/ADM cells was increased 5.37‑ and 6‑14‑fold compared with that in HepG2 cells. Furthermore, the expression levels in HepG2/ADM cells were decreased following U0126 treatment in a dose‑dependent manner. The expression of P‑gp and MRP1 in HepG2/ADM cells was increased 2.68‑ and 2.76‑fold compared with that in HepG2 cells. Furthermore, the expression levels in HepG/ADM cells were decreased following U0126 treatment in a dose‑dependent manner. The results of the present study indicate that the MEK inhibitor U0126 enhances sensitivity to chemotherapeutic drugs by downregulating P‑gp and MRP1 expression in resistant hepatocellular carcinoma cells. The combination of MEK inhibitor and conventional chemotherapeutic drugs may provide novel therapeutic prospects for the treatment of drug‑resistant hepatocellular carcinoma.

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