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 100 100 μg/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 μg/ml). Combined treatment with Trastuzumab (10 μg/ml) and CDDP (1 μg/ml) showed synergism. Our results were encouraging, and suggest a rationale for further investigations in a clinical setting. © 2002 Wiley-Liss, Inc.