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Establishment and partial characterization of an epirubicin-resistant gastric cancer cell line with upregulated ABCB1
Aledson Vitor Felipe1, Andrea Aparecida Moraes, Juliana de Oliveira
1Department of Medicine, Gastroenterology Division, Federal University, Sao Paulo, Brazil
Abstract:
Multidrug resistance (MDR) is a major impediment to successful chemotherapy of gastric cancer. Our aim was to establish an epirubicin-resistant cell subline (AGS/EPI) and to elucidate the mechanisms involved in acquired EPI resistance. The AGS/EPI cell subline developed by exposing parental AGS cells to stepwise increasing concentrations of EPI demonstrated 2.52-fold resistance relative to the AGS cell line, and mRNA expression of the ATP-dependent drug-efflux pump P-glycoprotein (Pgp), more recently known as ABCB1 protein, was similarly upregulated. An AGS/EPI cell subline could thus be effectively established, and MDR mechanism of these cells was shown to be related to the overexpression of mRNA of the ABCB1 gene.
Insights
Researchers developed epirubicin-resistant gastric cancer cells (AGS/EPI). This multidrug resistance (MDR) is linked to increased expression of the ABCB1 gene, which encodes P-glycoprotein (Pgp).
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Multidrug resistance (MDR) significantly hinders effective chemotherapy for gastric cancer.
- Understanding the mechanisms of acquired drug resistance is crucial for improving treatment outcomes.
Purpose of the Study:
- To establish an epirubicin-resistant gastric cancer cell subline (AGS/EPI).
- To investigate the molecular mechanisms underlying acquired epirubicin resistance in gastric cancer cells.
Main Methods:
- Parental AGS gastric cancer cells were exposed to stepwise increasing concentrations of epirubicin (EPI) to develop a resistant subline.
- Quantitative analysis was performed to determine the level of epirubicin resistance.
- Messenger RNA (mRNA) expression levels of the ATP-dependent drug-efflux pump P-glycoprotein (Pgp), also known as ABCB1 protein, were analyzed.
Main Results:
- The established AGS/EPI cell subline exhibited a 2.52-fold increase in epirubicin resistance compared to the parental AGS cells.
- A significant upregulation of mRNA expression for the ABCB1 gene was observed in the AGS/EPI cells.
- The findings indicate a correlation between ABCB1 gene overexpression and acquired epirubicin resistance.
Conclusions:
- An epirubicin-resistant gastric cancer cell subline (AGS/EPI) was successfully established.
- The primary mechanism contributing to acquired epirubicin resistance in this model involves the overexpression of the ABCB1 gene.
- These findings provide insights into MDR in gastric cancer and potential therapeutic targets.
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