Establishment and Partial Characterization of an Epirubicin-Resistant Gastric Cancer Cell Line with Upregulated ABCB1

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.

Cytotoxic Effect of Define Concentration of Yarrow (Achillea Millefolium) Extract Used in Iranian Traditional Medicine on Ags Human Gastric Cancer Cell-Line

“…The cytotoxicity of this plant against cancer cellline is so remarkable because of the genetically modification of these cells that harbor cDNAs encoding the proteins mediating common drug resistance activities such as mutation-activated epidermal growth factor receptor (EGFR) or which had knocked-out expression of tumor suppressor p53 47 . AGS cell-line with predescribed MDR against anti-cancer agents such as epirubicin which possesses up-regulated ATP-binding cassette B1 (ABCB1) 48 showed vulnerability against this extract which bolds the surprising results of current study even more. ABCB1 is a transporter protein with an effective activity for detoxifying in normal cells, but also its reverse activity against anticancer agents was reported during chemotherapy 49&50 .…”

Effects of Combinatorial Ubiquitinated Protein-Based Nanovaccine and STING Agonist in Mice With Drug-Resistant and Metastatic Breast Cancer

“…Previously, EPB-resistant gastric cancer cell lines were reported ( 41 ). In this study, we successfully established a new EPB-induced multi-drug-resistant cancer stem-like breast cancer cell line (4T1/EPB).…”

Distinct characterization of two vinorelbine-resistant breast cancer cell lines developed by different strategies

“…The expression of P-gp was found to be upregulated strongly in BC-DS and slightly in BC-TS, which may result in the difference of their maximum tolerated concentration to chemotherapeutic agents. Felipe et al (10) reported that P-gp was overexpressed in the epirubicin-resistant gastric cancer line they established using dose-stepwise incremental strategy. Monoclonal antibody, antagonist or depleting agent against P-gp is promising to optimize the therapeutic effect of vinorelbine.…”

“…Currently, the most typical method to establish a drug-resistant tumor cell line in vitro is stimulating tumor cells with a certain concentration of chemotherapy drug continuously while increasing the concentration gradually (8)(9)(10), but some studies state that this method has limitations (11,12). As the purpose to establish a drug-resistant tumor cell line is to provide a proper research tool for overcoming drug-resistance in clinic, the method should imitate the clinical chemotherapy setting, which commonly contains several cycles of 21 to 28 days discontinuous administration (13,14).…”