兰州大学机构库 >生命科学学院
ortho-Topolin Riboside 对人肝癌细胞SMMC-7721细胞的凋亡诱导机制
Alternative TitleMechanism of apoptosis induced by ortho-Topolin Riboside in the human hepatoma cell line SMMC-7721
王黎
Thesis Advisor郭光沁
2012-05-28
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name博士
Keywordortho-Topolin Riboside 凋亡 Akt ERK1/2 腺苷激酶 人肝癌细胞
Abstract天然形成的细胞分裂素ortho-Topolin Riboside (oTR)最近被报道有很强的抗肿瘤活性,但是相关的分子机制还没有报道。通过我们的实验结果发现oTR具有很强的抑制SMMC-7721肝癌细胞增殖的作用,并且诱导细胞的凋亡。当用oTR处理SMMC-7721细胞后,细胞内促凋亡蛋白Bax的蛋白水平上调,而抗凋亡蛋白Bcl-2 和 Bcl-xL的蛋白水平则下调,线粒体膜势能从而降低,进而导致Cytc释放到细胞浆中以及下游caspase-9 ,caspase-3蛋白酶的活化和死亡底物PARP的裂解。SMMC-7721细胞的凋亡效果可以被caspase广普抑制剂z-VAD-fmk和caspase-9特异性抑制剂z-LEHD-fmk部分阻断。另外oTR还可以抑制ERK1/2和 Akt信号通路的磷酸化,这些结果说明oTR诱导的SMMC-7721细胞的凋亡通过影响MAPK和Akt信号通路和内源性线粒体途径来产生。但是这种凋亡现象几乎可以完全被腺苷激酶抑制剂A-134974阻断,这说明细胞内的磷酸化是oTR对SMMC-7721细胞产生毒性所必需的。
Other AbstractThe naturally occurring cytokinin, ortho-Topolin Riboside (oTR), has been recently reported to have a strong anticancer effect. Moreover, oTR was shown to inhibit the activation of the extracellular signal-regulated kinase-1/2 (ERK1/2) as well as the Akt pathway. These results suggest that oTR interferes with the mitogen-activated protein kinase (MAPK) and Akt pathways and induces the apoptosis of human SMMC-7721 cells through the activation of intrinsic mitochondria-mediated pathways. However, the apoptosis was completely prevented when cells were treated with A-134974, an inhibitor of adenosine kinase, it indicated that the intracellular phosphorylation of oTR is necessary for its cytotoxic effects to SMMC-7721 cells.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/221907
Collection生命科学学院
Recommended Citation
GB/T 7714
王黎. ortho-Topolin Riboside 对人肝癌细胞SMMC-7721细胞的凋亡诱导机制[D]. 兰州. 兰州大学,2012.
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