8-氯腺苷酸诱导多发性骨髓瘤细胞凋亡及三氧化二砷的催化作用

8-chloroadenosine 3＇, 5＇-monophosphate induces apoptosis of multiple myeloma cells catalyzed by arsenic trioxide

目的探究8-氯腺苷酸（8．CI—cAMP）对多发性骨髓瘤（MM）细胞的作用和三氧化二砷（Asz0，）对其影响。方法以MM细胞株RPMI8226和U266细胞为体外模型，应用形态学和流式细胞术检测细胞DNA含量分布和细胞凋亡。以罗丹明染色检测线粒体跨膜电位，并以金氏公式评价8-Cl-cAMP和As：0，之间的协同效应。结果1～30mol／L8-C1-cAMP能够明显抑制RPMI8226和U266细胞的生长，并显著降低其细胞活力，呈时间和浓度依赖性。细胞形态学和流式细胞术分析显示，8-Cl-cAMP诱导骨髓瘤细胞凋亡并伴有线粒体跨膜电位的崩塌。As2O3能促进RPMI8226细胞凋亡，但与8-Cl-cAMP无协同作用。结论8-Cl-cAMP能够在体外有效地抑制MM细胞生长并诱导其凋亡，线粒体可能是8-Cl-cAMP诱导凋亡的靶点之一，As2O3催化了这个凋亡过程。

Objective To investigate the response of multiple myeloma （MM） cells to 8-chloroadenosine 3＇, 5＇-monophosphate （8-Cl-cAMP） and the impact of arsenic trioxide （As203） on the above reaction. Methods MM-derived cell lines RPMI8226 and U266 were used as in vitro models. Cell apoptosis was evaluated according to cellular morphology and DNA content measured by flow cytometry. Meanwhile, rhodamine 123 （Rhl23） staining and flow cytometry assay were used to detect the changes of mitochondrial transmembrane potentials （△ψm） in MM cells before and after the treatment. The synergic effects of 8-Cl-cAMP and As2O3 were evaluated by King＇ s formula. Results The 8-Cl-cAMP could induce growth inhibition of RPMI8226 and U266 ceils in dose and time-related manners. The 8-Cl-cAMP could trigger apoptosis and △ψm collapse in MM cells through cellular morphology and flow cytometry analysis. As2O3 accelerated 8-Cl-cAMP-mediated apoptosis of RPMI8226 cells, but there were few synergic effects observed. Conclusion 8-Cl-cAMP could induce cell proliferation inhibition and apoptosis in MM cells. Mitochondria may be one of targets in 8-Cl- cAMP-mediated apoptosis. Furthermore, As203 catalyzes 8-Cl-cAMP-induced apoptosis.