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• W2083004098 abstract "<b><i>Background/Aims:</i></b> Multidrug resistance (MDR) is a critical issue during chemotherapy of cancers. Phorbol 12-myristate 13-acetate (PMA), a diester of phorbol, is a typical activator of protein kinase C (PKC). In the present study, we investigated the effect of PMA on MDR and P-glycoprotein (P-gp) gene expression in K562/ADM cells. <b><i>Methods:</i></b> 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay was used to assess adriamycin (Adr)-induced cytotoxicity towards K562/ADM cells in the absence or presence of PMA. The intracellular accumulation of Adr was measured by determining the mean fluorescence intensity. The effect of PMA on P-gp activity was investigated by rhodamine-123 accumulation and efflux experiment. Protein expression and mRNA expression of P-gp in K562/ADM cells were determined by Western blot analysis and real-time qPCR, respectively. <b><i>Results:</i></b> Adr-induced cytotoxicity towards K562/ADM cells was significantly decreased by PMA at 5 μmol/l. Furthermore, intracellular Adr-associated mean fluorescence intensity was attenuated by 53.8% 1 h after exposure to PMA at 5 μmol/l compared with the control group (p < 0.05). A dose-dependent decrease of intracellular rhodamine-123 and increase of efflux activity of P-gp were also observed in K562/ADM cells incubation with PMA. In addition, P-gp mRNA and protein expression were significantly induced by PMA. <b><i>Conclusion:</i></b> Activation of PKC pathway by PMA can significantly induce expression and activity of P-gp, and thus decrease intracellular Adr level and strengthen MDR in K562/ADM cells." @default.
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• W2083004098 date "2013-01-01" @default.
• W2083004098 modified "2023-10-17" @default.
• W2083004098 title "Effect of Phorbol 12-Myristate 13-Acetate on Function and Gene Expression of P-Glycoprotein in Adriamycin-Resistant K562/ADM Cells" @default.
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• W2083004098 doi "https://doi.org/10.1159/000353774" @default.
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