Inhibition of mesothelioma cell growth in vitro by doxycycline

Malignant mesothelioma causes profound morbidity and nearly universal morta lity that is often refractory to conventional treatment modalities of aggre ssive surgery, radiotherapy, or chemotherapy. Doxycycline, a commonly used antibiotic, has anti-tumor activity against several malignancies, but its a nti-tumor effects on malignant mesothelioma have not been evaluated. We rep ort here that concentrations of doxycycline achievable in serum with typica l oral doses had cytostatic effects to varying extent on all eight of the m esothelioma cell lines studied but did not affect normal lung fibroblasts. Doxycycline inhibited the production of mitochondrial cytochrome c oxidase, especially in mesothelioma cells more sensitive to its cytostatic effects, and directly inhibited gelatinase A activity; both,of these activities are putative mechanisms for the cytostatic activity of doxycycline in other tu mor cells. Thus doxycycline may have a role as adjuvant therapy for maligna nt mesothelioma.