J 2015

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

ANNA, Konieczna, Vendula NOVÁKOVÁ, Jiřina MEDALOVÁ, Erceg SLAVEN, Martin KLABUSAY et. al.

Základní údaje

Originální název

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

Autoři

ANNA, Konieczna (203 Česká republika), Vendula NOVÁKOVÁ (203 Česká republika), Jiřina MEDALOVÁ (203 Česká republika, domácí), Erceg SLAVEN (203 Česká republika) a Martin KLABUSAY (203 Česká republika, garant)

Vydání

Klinicka onkologie Journal, 2015, 0862-495X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Kód RIV

RIV/00216224:14310/15:00086936

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

Thiazolidinedion; ABC Transporters; Lung Cancer

Štítky

Změněno: 13. 3. 2018 11:11, Mgr. Jiřina Medalová, Ph.D.

Anotace

V originále

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