线粒体和氧化砷诱导的肿瘤细胞凋亡的关系研究

In the project, we devoted our efforts to investigate the role of mitochondrion in arsenic trioxide (ATO)-induced apoptosis. The results showed that diamide, an opening reagent for the mitochondrial permeability transition pore (MPT), could reinforce ATO-induced apoptosis and mitochondrial transmembrane potentials(Djm) collapse, while the closing reagent of MPT, cycloporin A (CsA), strengthened the effects of ATO, indicating that ATO might induce cellular apoptosis and decrease the Djm by oxidating adenine nucleotide translocator(ANT), yet CsA could influence the efficacy of ATO through other pathway differing from that of MPT. Using the methods of proteomics, we found that cyclophilin A were modified by ATO. We also studied for the first time the effects of several in vivo methylated metabolites of ATO on APL cells, and proposed that the methylated status of arsenic was related to its in vivo efficacy. These researches further illustrated the machnism of ATO-induced apoptosis and would probably broaden the potentiality of the clinical application of ATO.

本项目拟在原有研究的基础上，以线粒体为切入点，通过分析离体线粒体在三氧化二砷诱导细胞凋亡中的作用、MPT对氧化砷效应的影响和砷是否与MPT蛋白结合等方面，继续深入研究三氧化二砷诱导肿瘤细胞凋亡的分子机制。这对于巩固具有我国特色的研究成果在国际上的领先地位，深入研究细胞凋亡分子机制等方面具有重要意义。