KML001과 Doxercalciferol의 급성 림프구성 백혈병 세포에 대한 시너지적 항백혈병 효과

Abstract

Abstract Introduction: KML001 (NaAsO2, Sodium metaarsenite, KOMINOX), a kind of arsenic compound, has shown promising efficacy in non-Hodgkins lymphoma (NHL) both in vitro and in vivo. However, its antileukemic effect on acute lymphoid leukemia (ALL) was still not totally clear. Here, in our research, the antileukemic effect of KML001 on acute lymphoid leukemia (ALL) and its mechanism of action were investigated. And also, we tested the possibility of synergy of KML001 with Doxercalciferol, a vitamin D2 derivative. Methods: To study the antileukemic effect of KML001 on ALL, we used MTT assay to test its cytotoxicity, flow cytometry to observe cell cycle arrest and cell apoptosis after treating two types of ALL cells, CCRF-CEM and Molt-4, with KML001. The synergistic effect of KML001 and Doxercalciferol on ALL cells was identified by MTT, flow cytometry. And finally, we did experiments like western blot, flow cytometry and intracellular calcium analysis to explore the possible reasons of this synergistic effect of two different drugs. Results: KML001 inhibited cell proliferation in two types of ALL cell lines. Exposure of ALL cells to KML001 induced apoptosis in a time-dependent manner. KML001 caused cell cycle arrest at G2/M phase instead of G0/G1 phase shown in other leukemia cells. In addition, we found that a combination of KML001 with Doxercalciferol showed a synergistic effect on ALL cell lines and this could be attributed to its different mechanism concerning apoptosis, cell cycle arrest and calcium relevant pathway. Conclusions: Our findings demonstrated KML001 could be a promising antileukemic agent especially when it is combined with Doxercalciferol in ALL treatment.