The effects of a novel MEK inhibitor PD184161 on MEK-ERK signaling and growth in human liver cancer
The effects of a novel MEK inhibitor PD184161 on MEK-ERK signaling and growth in human liver cancer
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DOI：
10.1593/neo.05373
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发表时间：
2006-01-01
期刊：
影响因子：
4.8
通讯作者：
Sebolt-Leopold, Judith S.
中科院分区：
文献类型：
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作者：
Klein, Patrick J.;Schmidt, C. Max;Sebolt-Leopold, Judith S.
MEK-ERK生长信号通路在人肝细胞癌中起重要作用。为了评估该途径在肝癌中的靶向性，我们利用人肝癌细胞(HepG2、Hep3B、PLC和SKHep)和体内人肿瘤移植瘤表征了一种新型的口服活性MEK抑制剂PD184161。PD184161以时间和浓度依赖的方式抑制MEK活性(IC50=10-100 nM)，比PD098059或U0126更有效。PD184161以时间和浓度依赖的方式抑制细胞增殖和诱导细胞凋亡。在体内，口服PD184161 3-12小时后，移植瘤P-ERK水平显著降低(P
The MEK-ERK growth signaling pathway is important in human hepatocellular carcinoma (HCC). To evaluate the targeting of this pathway in HCC, we characterized a novel, orally-active MEK inhibitor, PD184161, using human HCC cells (HepG2, Hep3B, PLC, and SKHep) and in vivo human tumor xenografts. PD184161 inhibited MEK activity (IC50 = 10-100 nM) in a time- and concentration-dependent manner more effectively than PD098059 or U0126. PD184161 inhibited cell proliferation and induced apoptosis at concentrations of >= 1.0 mu M in a time- and concentration-dependent manner. In vivo, tumor xenograft P-ERK levels were significantly reduced 3 to 12 hours after an oral dose of PD184161 (P