埃罗替尼
癌症研究
酪氨酸激酶
医学
药理学
细胞凋亡
表皮生长因子受体
细胞周期检查点
盐酸厄洛替尼
肝细胞癌
细胞周期
细胞生长
多西紫杉醇
癌症
酪氨酸激酶抑制剂
内科学
化学
受体
生物化学
作者
Alexander Huether,Michael Höpfner,Andreas Sutter,Detlef Schuppan,Hans Scherübl
标识
DOI:10.1016/j.jhep.2005.02.040
摘要
Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. In light of the very poor 5-year-survival new therapeutic approaches are urgently needed. Recently, evidence has been accumulated that the epidermal growth factor receptor (EGFR) is a promising target for cancer therapy. Several reports indicate that EGFRs are expressed frequently in HCC, most likely contributing to the aggressive growth characteristics of these tumors.Erlotinib, an inhibitor of EGFR-tyrosine kinase, potently suppresses the growth of various tumors, but its effect on HCC remains to be explored. We therefore studied the antineoplastic potency of erlotinib in human HCC cells (Huh-7 and HepG2 cell lines).We show that erlotinib inhibited HCC growth in a time- and dose-dependent manner. Moreover erlotinib treatment induced apoptosis and resulted in a dose-dependent arrest at the G1/S checkpoint of the cell cycle. Combining erlotinib with doxorubicin or docetaxel or SN-38 resulted in additive or even synergistic antiproliferative effects.Our data demonstrate that in human HCC cells the inhibition of EGFR-tyrosine kinase by erlotinib induces growth inhibition, apoptosis and cell cycle arrest. Additionally, erlotinib enhances the antineoplastic activity of conventional cytostatic drugs. Thus, inhibiting EGFR-tyrosine kinase appears to be a promising treatment strategy in HCC.
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