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ABCG2 gene amplification and expression in esophageal cancer cells with acquired adriamycin resistance
Liang Liu1, Lian Fu Zuo1, Jian Wen Guo1
1Department of Flow Cytometry Analysis, Tumor Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
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.
Insights
Multidrug resistance (MDR) in esophageal cancer is linked to increased expression of ATP-binding cassette transporter G2 (ABCG2). This study found higher ABCG2 levels and drug efflux in resistant cells, suggesting ABCG2
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Chemotherapeutic resistance is a major cause of cancer treatment failure.
- Multidrug resistance (MDR) is often mediated by drug efflux transporters like ATP-binding cassette transporter G2 (ABCG2).
- Mechanisms of MDR in esophageal cancer remain largely undescribed.
Purpose of the Study:
- To investigate the role of ABCG2 in adriamycin (ADM)-resistant esophageal cancer cells.
- To characterize the adriamycin-resistant esophageal cancer subline Eca109/ADM.
- To determine the correlation between ABCG2 expression and MDR in esophageal cancer.
Main Methods:
- Generation of an adriamycin-resistant esophageal cancer cell line (Eca109/ADM) through stepwise selection.
- Assessment of ADM resistance fold-change compared to the parental cell line.
- Detection of ABCG2 gene and protein expression using RT-PCR, flow cytometry, and western blotting.
- Evaluation of drug efflux effects via flow cytometry.
Main Results:
- The Eca109/ADM subline exhibited a 3.29-fold increase in resistance to ADM.
- ABCG2 gene and protein expression levels were significantly elevated in Eca109/ADM cells compared to Eca109 cells.
- Increased drug efflux was observed in the Eca109/ADM cells, correlating with higher ABCG2 expression.
Conclusions:
- Overexpression of ABCG2 in esophageal cancer cells contributes to adriamycin resistance.
- Elevated ABCG2 levels facilitate drug efflux, playing a key role in the development of esophageal cancer MDR.
- These findings highlight ABCG2 as a potential therapeutic target for overcoming MDR in esophageal cancer.
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