Lentivirus-mediated osteosarcoma-selective chemogene therapy employing the human folylpolyglutamate synthetase/methotrexate system and the human osteocalcin promoter

The antifolate methotrexate (MTX) is an important chemotherapeutic agent for treatment of osteosarcomas. This drug usually converts intracellulary into polyglutamate derivates by the enzyme folylpolyglutamate synthetase (FPGS). MTX polyglutamates show an enhanced and prolonged cytotoxicity in comparison to the monoglutamate. We, therefore, investigated in the present study if transfer of the human fpgs gene to osteosarcoma cells may augment their MTX sensitivity. For this purpose, we employed the human osteocalcin (OC) promoter which had shown marked osteosarcoma specificity in promoter studies using different l…