MEK inhibition enhances bleomycin A5-induced apoptosis in an oral cancer cell line: signaling mechanisms and therapeutic opportunities.

doi:10.1111/j.1600-0714.2004.00006.x

中山醫學大學機構典藏 CSMUIR > 口腔醫學院 > 牙醫學系暨碩士班 > 期刊論文 > Item 310902500/10605

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: https://ir.csmu.edu.tw:8080/ir/handle/310902500/10605

题名:	MEK inhibition enhances bleomycin A5-induced apoptosis in an oral cancer cell line: signaling mechanisms and therapeutic opportunities.
作者:	Yang, LC Yang, SH Tai, KW Chou, MY Yang, JJ
贡献者:	中山醫學大學
日期:	2004
上传时间:	2015-04-10T07:23:34Z (UTC)
摘要:	BACKGROUND: Bleomycin A5 is an anti-neoplastic glycoprotein antibiotic used for the treatment of various cancers. Previous work has shown that bleomycin A5 exerts its apoptotic effects on tumor cells. This was to study the signal transduction pathways that might exert the apoptotic effects of bleomycin A5 on tumor cells, as well as to examine the possibility of lower dosing of such drug in combinative treatment with other compounds in vitro. METHODS: Bleomycin A5 was applied on a human oral epidermoid carcinoma cell line, human oral epidermoid carcinoma (KB), and the apoptotic activity was determined by the presence of DNA fragmentation and 4,6-diamidino-2-phenylindole (DAPI) nuclear staining. The signal transduction pathway was measured through Western blotting and in vitro kinase assay. RESULTS: The apoptotic effect was associated with the sustained activation of c-Jun N-terminal kinases (JNK) and the inhibition of extracellular signal-regulated kinases1 (ERK1) and -2 activities, suggesting that JNK plays a positive role in the death process. ERK1 and -2 might exert a protection pathway from cell death. Here, it was determined that a combination treatment of bleomycin A5 and the MAP kinase-ERK kinase (MEK) inhibitor, PD98059, could lead to enhanced apoptosis. The activities of ERK1 and -2 are required for cell survival signaling using stable cell clones expressing MEK1. Upon bleomycin A5 treatment, cells expressing MEK1 exhibited significant delays in the onset of apoptosis, where the presence of MEK1 inhibitor enhanced cell death. Moreover, the increased activity of ERK1 and -2 coincided with cell survival. The survival signals exerted by MEK1 most likely result from the activation of ERK1 and -2. CONCLUSIONS: The apoptosis enhancement through such combinative treatment in vitro has revealed new therapeutic opportunities and elucidated mechanisms contributing to the efficacy of existing anti-cancer treatments.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/10605
關聯:	J Oral Pathol Med. 2004 Jan;33(1):37-45.
显示于类别:	[牙醫學系暨碩士班] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
index.html	報導	0Kb	HTML	370	检视/开启

检视Licence

在CSMUIR中所有的数据项都受到原著作权保护.

TAIR相关文章

数据加载中.....