Chemosensitivity of newly established human malignant pleural mesothelioma cells: Significant growth inhibition by amrubicin, a novel 9-aminoanthracycline, or cyclooxygenase 2 inhibitor

Abstract

e19060 Background: Malignant pleural mesothelioma is asbestos-related malignancy that is highly resistant to current therapeutic modalities. Survival of patients with malignant mesothelioma is very poor, especially in advanced stage, regardless of a recent advancement of chemotherapeutical modalities of combination with cisplatin and antifolate. Methods: Eleven cell lines derived from malignant mesothelioma were established in our laboratory. Chemosensitivity of these cell lines to nine chemotherapeutic drugs (cisplatin, vinorelbine, irinotecan, gemcitabine, pemetrexed, gefitinib, erlotinib, and amrubicin and its active in vivo substance, amrubicin-13-OH) and four cyclooxygenase 2 inhibitors was tested by MTT assay. Results: Anti-cancer agents, cisplatin, vinorelbine, gemcitabine, gefitinib, or erlotinib, showed little growth inhibition, and pemetrexed and irinotecan showed modest growth inhibition in malignant mesothelioma cells, whereas amrubicin-13-OH showed strong growth inhibition. Cyclooxygenase 2 inhibitors inhibit proliferation of malignant mesothelioma cells in a dose-dependent manner: modest growth inhibition at clinically achievable low concentrations and complete growth inhibition at clinically achievable high concentrations by intrapleural instillation. In addition, enhanced growth suppression was obtained by using amrubicin-13-OH in combination with cyclooxygenase 2 inhibitor. Conclusions: Our study suggests that amrubicin can inhibit proliferation of malignant mesothelioma cells. In addition, the use of a cyclooxygenase 2 inhibitor may be a promising therapeutic approach in the treatment of mesothelioma, because previous studies indicated the presence of increased cyclooxygenase 2 expression in malignant mesothelioma, which is notoriously resistant to chemotherapy. No significant financial relationships to disclose.