Tamoxifen Suppresses the Growth of Malignant Pleural Mesothelioma Cells.

Abstract

Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy most often associated with exposure to asbestos. Recent evidence points to oestrogen receptor (ER)-β having a tumour-suppressor role in MPM progression, and this raises the question of whether selective modulators of ERs could play a role in augmenting MPM therapy. We investigated the action of tamoxifen in inhibiting the growth and modulating the cisplatin sensitivity of four MPM cell lines. Tamoxifen inhibited the growth of MPM cells and also modulated their sensitivity to cisplatin. The MPM cell lines expressed ERβ, but the actions of tamoxifen were not blocked by antagonism of nuclear ERs. Tamoxifen treatment repressed the expression of cyclins by MPM cells, resulting in cell-cycle arrest and caspase-3-coupled apoptosis signaling. The ER-independent actions of tamoxifen on MPM cell proliferation and cell-cycle progression may have clinical benefits for a subset of patients with MPM.