Role of a guanine nucleotide-exchange protein, ARF-GEP100, in the doxorubicin resistance of K562 human leukemia cells

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It has been already revealed that ARF-GEP100 (p100) preferentially activates ARF (ADP-ribosylation factor) in vitro and regulated various cell functions. In contrast, P-glycoprotein (Pgp) transports a broad range of anticancer drugs out of the cells. The inhibition of Pgp is expected to circumvent the Pgp-mediated drug resistance. In this study, we examined whether p100 may affect the expression of Pgp using the Doxorubicin (DOX)-resistant K562 cells. The expression level of p100 increased, accompanied with Pgp expression. Interestingly, the expression of p100 was increased in the cell membrane fraction. Furthermore, anti-Pgp antibody immunoprecipitated p100 in DOX resistant cell lysate. The DOX resistant cells treated with ARF6 siRNA were investigated for expression level of Pgp and p100. However, the expression of Pgp and p100 was not changed.Collectively, these observations suggest that p100 may be involved in the expression and activation of Pgp to induce the DOX resistance.