ABCG2 gene amplification and expression in esophageal cancer cells with acquired adriamycin resistance

Abstract

Abstract. Resistance to chemotherapeutic agents is the main reason for treatment failure in patients with cancer. The primary mechanism of multidrug resistance (MDR) is the overexpression of drug efflux transporters, including ATP-binding cassette transporter G2 (ABCG2). To the best of our knowledge, the MDR mechanisms of esophageal cancer have not been described. An adriamycin (ADM)-resistant subline, Eca109/ADM, was generated from the Eca109 esophageal cancer cell line by a stepwise selection in ADM from 0.002 to 0.02 ng/µl. The resulting subline, designated Eca109/ADM, revealed a 3.29-fold resistance against ADM compared with the Eca109 cell line. The ABCG2 gene expression in the Eca109/ADM cells was increased compared with that of the Eca109 cells. The cellular properties of the Eca109/ADM cells were detected by reverse transcription polymerase chain reaction (RT-PCR), flow cytometry and western blotting. The ABCG2 expression levels were detected by RT-PCR and flow cytometry, and the drug efflux effect was detected by flow cytometry. The present study detected the correlation between ABCG2 and the multidrug resistance of esophageal cancer. ABCG2 gene expression and the drug efflux effect of the Eca109/ADM cells were increased compared with those of the Eca109 cells. Collectively, the results of this study indicated that the overexpression of ABCG2 in the Eca109/ADM cells resulted in drug efflux, which may be responsible for the development of esophageal cancer MDR.

CM082 Enhances the Efficacy of Chemotherapeutic Drugs by Inhibiting the Drug Efflux Function of ABCG2

“…4 In particular, ABCB1, ABCG2, and ABCC1 are considered to be major contributors to MDR. 5 As a semi-transporter protein encoded by the ABCG2 gene at human chromosome 4q22-23, ABCG2 is highly expressed in various kinds of cancer cells, such as breast cancer, 6 esophageal cancer, 7 nasopharyngeal cancer, 8 acute myeloid leukemia, 9 non-small-cell lung cancer, 10 and renal malignancy. 11 In addition, ABCG2 was associated with drug resistance and poor prognosis of the patients, 6,11,12 while the inhibition of ABCG2 expression could potentially reverse MDR.…”

VS-4718 Antagonizes Multidrug Resistance in ABCB1- and ABCG2-Overexpressing Cancer Cells by Inhibiting the Efflux Function of ABC Transporters

“…The ABC transporters significantly decrease the intracellular concentration of certain anticancer drugs by pumping substrate drugs out of cancer cells, which becomes a major impediment to chemotherapy. It is well documented that the expression of ABC transporters are associated with the level of response of chemotherapy and the progression of malignancy (Liu et al, 2013 , 2014 ; Ali and Elsalakawy, 2014 ; Xie et al, 2014 ; Yang et al, 2015 ). Thus, inhibiting the efflux function of ABC transporters is of great importance to enhance the efficacy of chemotherapy (Shukla et al, 2008 ).…”

Resistin Induces Multidrug Resistance in Myeloma By Inhibiting Cell Death and Upregulating ABC Transporter Expression

“…Overexpression of ABC transporters has been shown to increase ATP-driven efflux of chemotherapy drugs from tumor cells and thus decrease intracellular drug accumulation, leading to drug resistance. 7 To investigate the impact of resistin on ABC-driven efflux of chemotherapy drugs in myeloma cells, ARP-1 or MM.1S cells were cultured with or without the addition of resistin. The cells were then labeled with the eFluxx-ID gold fluorescent dye and analyzed by flow cytometry.…”

“…5,6 Its expression is upregulated in a variety of malignancies, in which it may produce resistance to chemotherapeutic agents. [6][7][8] ABCC5, also known as multidrug resistance protein 5, belongs to D espite advances in therapy, multiple myeloma remains incurable, with a high frequency of relapse. This suggests the need to identify additional factors that contribute to drug resistance.…”