科研之友
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摘要
Norcantharidin (NCTD) is an effective anti-tumor drug developed by China independently. It has been widely used for clinical therapy especially in digestive tract cancers. It was found that NCTD can induce M arrest and apoptosis in a dose- and time-dependent manner in BGC-823 cell line. In order to reveal the molecular mechanism by which NCTD actions systemically, a comparative analysis of proteomic profiling was conducted between control cells and NCTD treated cells by 2-D and mass spectrum. The results indicated that mitochondrial heat shock protein CH60, ATP synthase d subunit, ER glucose-regulated protein GRP78, mitochondrial Hsp70 related factor GRPE1, SH3 domain-binding glutamic acid-rich-like protein SH3L3 and Histone-binding protein RBBP4 may involve in the antitumor function of NCTD. The result suggested that NCTD might induce caspase-3 dependent apoptosis through promoting the expression of mitochondrial heat shock protein and p53. NCTD can promote the apoptosis by inhibiting the activity of ERK after inducing ER stress. The combinational treatment of BGC-823 cells with oligomycin A, an inhibitor of mitochondrial ATP synthase, and NCTD inhibited the growth of BGC-823 cells more evidently compared with single drug treatment. This result confirmed that NCTD can suppress the growth of BGC-823 by inhibiting the activity of mitochondrial ATP synthase.
- 出版日期2009-9
- 单位北京市肿瘤防治研究所; 北京大学; 北京师范大学
