Publication details

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



Year of publication 2015
Type Article in Periodical
Magazine / Source Klinicka onkologie Journal
MU Faculty or unit

Faculty of Science

Field Oncology and hematology
Keywords Thiazolidinedion; ABC Transporters; Lung Cancer
Description ATP binding cassette (ABC) transporters related to multidrug resistance (MDR) actively efflux various xenobiotics 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 PPARgama 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 PPARgama 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 PPARgama 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 PPARgama agonists treatment using quantitative reverse transcription real-time PCR (qRT-PCR). All three PPARgama agonists serve as substrates to at least one ABC transporter under study.PPARgama activation correlates with the upregulation of PTEN, which may modulate the expression of ABC transporters via 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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