Promotion of all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia cells by Bufalin

All-trans retinoic acid (ATRA) has been shown as a promising agent for the treatment of acute promyelocytic leukemia (APL). However, the clinical application of ATRA is limited by the resistance of APL to ATRA-induced differentiation. Bufalin is a steroid isolated from Chan’su and could induce leukemia cell differentiation. This study is aimed to determine whether bufalin treatment could promote ATRA-induced differentiation of APL cell lines and primary cells. The cell surface differentiation marker CD11b, nitro blue tetrazolium (NBT) reduction and morphological changes in the cells were examined. The results showed that bufalin promoted ATRA-induced differentiation of APL primary cells and NB4 cell line, although low dose of bufalin alone had no direct effects on APL cell differentiation. In addition, bufalin and ATRA had synergistic effects to down-regulate survivin expression in NB4 cells. Taken together, these data suggest that bufalin is a potential regimen to be used in combination with ATRA to promote the differentiation of APL cells, which could achieve better therapy efficacy.   Key words: Bufalin, all-trans retinoic acid, surviving, acute promyelocytic leukemia,differentiation.