Hepatocyte Growth Factor Sensitizes Human Ovarian Carcinoma Cell Lines to Paclitaxel and Cisplatin

Andrea Rasola, Sergio Anguissola, Norma Ferrero, Daniela Gramaglia, Antonella Maffe, Piera Maggiora, Paolo M. Comoglio, M. Flavia Di Renzo

Research output: Contribution to journalArticle

Abstract

The hepatocyte growth factor (HGF) receptor, encoded by the MET oncogene, is expressed in ∼70% of human ovarian carcinomas and overexpressed in 30% of cases. Because HGF is known to protect cells from apoptosis, we investigated whether receptor expression modifies ovarian cancer cell response to chemotherapy. The apoptotic effect of the frontline chemotherapeutic drugs paclitaxel and cisplatin on cells treated with HGF was studied. In ovarian cancer cell lines, pretreatment with HGF surprisingly enhances the apoptotic response to low doses of paclitaxel and cisplatin. HGF empowers specifically the intrinsic apoptotic pathway, whereas it protects cells from extrinsic Fas-induced apoptosis. Chemotherapy sensitization is specific for HGF because another growth factor (e.g., epidermal growth factor) increases ovarian cancer cell survival. In nonovarian cancer cell models, as expected, HGF provides protection from drug-induced apoptosis. These data show that HGF sensitizes ovarian carcinoma cells to low-dose chemotherapeutic agents. This suggests that HGF may be used to improve response to chemotherapy in a set of human ovarian carcinomas molecularly classified based on the MET oncogene expression.

Original languageEnglish
Pages (from-to)1744-1750
Number of pages7
JournalCancer Research
Volume64
Issue number5
DOIs
Publication statusPublished - Mar 1 2004

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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