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      Thiazolidinediones Regulate the Level of ABC Transporters Expression on Lung Cancer Cells.

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          Abstract

          ATP binding cassette (ABC) transporters related to multidrug resistance (MDR) actively efflux various xenobio-tics from the cells across the cell membrane and decrease a drugs efficiency. Lung cancer is the leading cause of death among all types of cancer in the Czech Republic, and its incidence is still rising. Ciglitazone, rosiglitazone and troglitazone belonging to PPARγ agonist family (formerly used in diabetes mellitus treatment) were selected to investigate their capability to influence expression of ABC transporters on lung cancer cells. Therefore, the effect of PPARγ of agonists on transcription of following ABC transporters was investigated: multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP). We have investigated if these PPARγ agonists are substrates of ABC transporters using HL60 and HL60 derived cell lines (HL60-MDR1, HL60-MRP1, PLB-BCRP) by cytotoxicity test WST-1. We have mapped the changes in mRNA expression level of those transporters in A549 and HEK293 cells after PPARγ agonists treatment using quantitative reverse transcription real-time PCR (qRT-PCR). All three PPARγ agonists serve as substrates to at least one ABC transporter under study. PPARγ activation correlates with up-regulation of PTEN which may modulate the expression of ABC transporters through PI3K/ Akt signaling pathway. We have shown that rosiglitazone and troglitazone inhibit mRNA expression of MDR1 transporter in both cell lines whereas the expression of MRP1 in HEK293 cell was up-regulated after rosiglitazone treatment and the expression of MDR1 was upregulated after ciglitazone treatment.

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          Author and article information

          Journal
          Klin Onkol
          Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti
          0862-495X
          0862-495X
          2015
          : 28
          : 6
          Article
          56837
          26673993
          6737e24d-85a6-4f42-98b5-dd7a89f6431a
          History

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