Synergistic effect of the anti-HER-2/neu antibody and cisplatin in immortalized and primary mesothelioma cell lines

J Cell Physiol. 2002 Oct;193(1):37-41. doi: 10.1002/jcp.10150.

Abstract

Malignant mesothelioma (MM) still remains a therapeutic and diagnostic problem to which new therapeutic perspectives are being continuously tried and tested. Three different primary cultures (MMGe-1, MES MM 98, and MES 1) and one immortalized cell line (MSTO 211 H) of human MM were studied in order to evaluate the HER-2/neu expression. Three out of four cell lines showed a different level of c-erbB-2 expression, the highest being detected on the MSTO 211 H cell line (fibroblastic phenotype), whereas MMGe-1 resulted negative. The effect of the anti-HER-2/neu antibody (Trastuzumab) alone, and in combination with cisplatin (CDDP) at different doses (ranging from 0.1 to 100 microg/ml), was studied on all the c-erB-2 positive cell lines. Trastuzumab was able to inhibit cell proliferation in a time-dependent manner, with growth inhibition also obtained at low concentrations (0.1-1 microg/ml). Combined treatment with Trastuzumab (10 microg/ml) and CDDP (1 microg/ml) showed synergism. Our results were encouraging, and suggest a rationale for further investigations in a clinical setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cisplatin / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Drug Synergism
  • Humans
  • Mesothelioma / drug therapy*
  • Mesothelioma / pathology
  • Pleural Neoplasms / drug therapy*
  • Pleural Neoplasms / pathology
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / immunology
  • Time Factors
  • Trastuzumab
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Receptor, ErbB-2
  • Trastuzumab
  • Cisplatin