ST3 β-galactoside α-2,3 sialyltransferase 5 inhibited the multidrug resistance of leukemia NB4 cell line
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Abstract:
Objective:To confirm the effect of ST3 β-galactosideα-2,3 sialyltransferase 5 (ST3GAL5) on drug resistance of AML in vivo and in vitro through studying the differential expression of ST3GAL5 between acute myeloid leukemia (AML) NB4 cell line and its drug-resistant cell line NB4/ADR. Methods: The expressions of ST3GAL5 in AML cell lines were detected by Real-time PCR and Western blotting assays. Expressions of ST3GAL5 in the cells were specifically regulated to increase or decrease. Before and after the interferences, Changes of sensitivities to chemotherapy drugs and activation of PI3K/Akt signaling pathway in the NB4 and NB4/ADR cells in vivo and in vitro were examined by MTT assay and experiments with xenograft mouse model. Results: ST3GAL5 was highly expressed in NB4 cell line but low expressed in its drug-resistant cell line NB4/ADR. Drug sensitivity and PI3K/Akt signaling pathway molecules of NB4/ADR cells in which expressions of ST3GAL5 were specifically up-regulated respectively increased and decreased (all P<0.05). Contrarily, drug sensitivity, PI3K/Akt signaling pathway molecules and P-gp of NB4 cells in which expressions of ST3GAL5 were down-regulated respectively decreased and increased. Conclusion: There were obvious differences of ST3GAL5 expressions between AML cell and its drug-resistant cell lines. These characteristic alterations are associated with multidrug resistance in AML, which is probably achieved through ST3GAL5 mediated-PI3K/Akt signaling pathway and alteration of P-gp expression.
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Project supported by the Natural National Science Foundation of China (No. 81271910)