Effects of ATP-competitive GSK-3 inhibitor on multidrug resistance of human esophageal squamous-cell carcinoma cells

AIM: To study the changes and correlations of β-catenin, multidrug resistance-associated protein 2 (MRP2), P-glycoprotein (P-gp), Bcl-2 and the free ATP level in esophageal squamous-cell carcinoma (ESCC) cell line EC-109 induced by ATP-competitive glycogen synthase kinase(GSK-3) inhibitor 6-bromoindirubin-3'-oxime (BIO). METHODS: The methods of flow cytometry, immunofluorescence, cytochemistry and ATP assay were used to study the expression levels of MRP2, P-gp, β-catenin and Bcl-2, the efflux capability of ATP-binding cassette (ABC) transporters, and the free ATP level in ESCC cells. RESULTS: After induced by BIO, up-regulation of β-catenin and Bcl-2 expression in cytoplasm and accumulation of β-catenin in nucleus were found in ESCC cells. The expression of MRP2 was up-regulated in cytoplasm and cell membrane. On the contrary, the expression of P-gp was down-regulated in cytoplasm and cell membrane. The free ATP level and the efflux capability of ABC transporters increased in ESCC cells. CONCLUSION: The multidrug resistance of ESCC cells in enhanced by BIO treatment.