Role of artesunate in resistance-reversal of esophageal cancer Eca109/ADM cells to doxorubicin
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Abstract:
Objective:To explore the role of artesunate (Art) in resistance-reversal of Eca109/ADM cells and the related mechanism. Methods:The present study was divided into 4 groups: normal saline (NS) control group, Art (0.1 μmol/L) group, ADM (0.2 μg/ml) group, and Art (0.1 μmol/L)+ADM (0.2 μg/ml) group. The apoptosis rate, ADM content and ABCG2 (ATP-binding cassette transporter G2) protein expression in Eca109/ADM cells were detected by flow cytometry 48 h after treated with Art, ADM, and Art+ADM. ABCG2 protein expression in Eca109/ADM cells was further examined by Western blotting analysis. Results:The apoptosis rate of Eca109/ADM cells in Art+ADM group was (12.89±0.87)%, being significantly higher than that in the Art group (1.58±0.12)%, ADM group (6.55±090)% and NS group (1.44±0.10)% (P<0.05). Art increased the sensitivity of Eca109/ADM cells to ADM. Flow cytometry results showed that the ABCG2 protein expression in Eca109/ADM cells of Art+ADM group (644.60±3.21) was significantly lower than that in ADM group (659.15±4.59) and NS group (658.14±6.88) (P<0.05), but was similar to that in Art group (644.31±3.96) (P>0.05). Western blotting analysis results were consistent with those detected by flow cytometry. The ABCG2 protein expression of Eca109/ADM cells in Art group (0.70±0.02) was significantly decreased compared with NS group (0.80±0.03) (P<0.05), and that in Art+ADM group (0.71±0.04) was also decreased compared with ADM group (0.81±0.05) (P<0.05). The ADM content of Eca109/ADM cells in Art+ADM group was significantly higher than those in Art, ADM and NS groups (848.02±5.04 vs 763.29±4.02, 800.25±3.84, 763.88±2.03; P<0.01). Conclusion: Art can decrease ABCG2 protein expression and increase ADM content in Eca109/ADM cells, and it can also reverse the drug resistance of Eca109/ADM cells.
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Project supported by the Natural Science Foundation of Heibei Province (No. C2007001060), and the Key Specific Discipline Foundation of Higher Institutions of Hebei Province (No. \[2005\]52)