Autocrine inhibition of chemotherapy response in human liver tumor cells by insulin-like growth factor-II
Autocrine inhibition of chemotherapy response in human liver tumor cells by insulin-like growth factor-II
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DOI：
10.1016/j.canlet.2003.10.018
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发表时间：
2004-03-31
期刊：
影响因子：
9.7
通讯作者：
Schirmacher, P
中科院分区：
文献类型：
--
作者：
Lund, P;Schubert, D;Schirmacher, P
胰岛素样生长因子（IGF）-II在实验性和人类肝细胞癌（HCC）中经常过表达，并与肿瘤生长增加相关。我们分析了IGF-II是否影响人肝癌细胞的化疗反应和凋亡。三种肝肿瘤细胞系高表达IGF-II，并通过分泌过量的IGF-II以自分泌方式支持其生长。IGF-II的中和作用显著增加了对化疗药物顺铂和依托泊苷的反应，特别是在较低的细胞抑制剂量下。虽然IGF-II的阻断并没有增加指数生长培养物中的自发性细胞死亡，但在融合生长和化疗的条件下发现细胞死亡增加。因此，在HCC细胞中，IGF-II是一种相关的促肿瘤生长因子，可显著降低对细胞凋亡和化疗治疗的敏感性。因此，干扰IGF-II活性可能会改善HCC对其他低效化疗药物的反应。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Insulin-like Growth Factor (IGF)-II is frequently overexpressed in experimental and human hepatocellular carcinomas (HCCs) and has been correlated with increased tumor growth. We have analyzed, whether IGF-II affects chemotherapy response and apoptosis in human liver tumor cells. Three liver tumor cell lines highly expressed IGF-II and supported their growth in an autocrine manner by secreting excessive amounts of IGF-II. Neutralization of IGF-II significantly increased response to the chemotherapeutic agents cisplatin and etoposide especially at lower, cytostatic doses. While blocking of IGF-II did not increase spontaneous cell death in exponentially growing cultures, increased cell death was found under conditions of confluent growth and chemotherapy. Thus in HCC cells, IGF-II is a relevant protumorigenic growth factor that significantly reduces susceptibility to apoptosis and chemotherapeutic treatment. Therefore interference with IGF-II activity may improve response of HCCs to otherwise inefficient chemotherapeutic agents. (C) 2003 Elsevier Ireland Ltd. All rights reserved.