Autocrine inhibition of chemotherapy response in human liver tumor cells by insulin-like growth factor-II

Cancer Lett. 2004 Mar 31;206(1):85-96. doi: 10.1016/j.canlet.2003.10.018.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Autocrine Communication*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Division / drug effects
  • Cisplatin / pharmacology
  • Etoposide / pharmacology
  • Humans
  • In Situ Nick-End Labeling
  • Insulin-Like Growth Factor II / pharmacology*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Insulin-Like Growth Factor II
  • Etoposide
  • Cisplatin