Synergistic effect of the anti-HER-2/neu antibody and cisplatin in immortalized and primary mesothelioma cell lines.
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.
Toma
Salvatore
S
Department of Oncology, Biology and Genetics, University of Genoa, Italy. toma@cba.unige.it
Colucci
Lucia
L
Scarabelli
Linda
L
Scaramuccia
Angelo
A
Emionite
Laura
L
Betta
Pier Giacomo
PG
Mutti
Luciano
L
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D013997:Time Factors; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002945:Cisplatin; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab