Marilù Fanelli, Claudia Maria Hattinger, Serena Vella, Elisa Tavanti, Francesca Michelacci, Beth Gudeman, Daryl Barnett, Piero Picci and Massimo SerraPages 261-274 (14)
By using a group of 6 drug-sensitive and 20 drug-resistant human OS cell lines, the most relevant transporter which proved to be associated with the degree of drug resistance in OS cells, in addition to ABCB1, was ABCC1. We therefore evaluated the in vitro activity of the orally administrable ABCB1/ABCC1 inhibitor CBT-1® (Tetrandrine, NSC-77037). We found that in our OS cell lines this agent was able to revert the ABCB1/ABCC1-mediated resistance against doxorubicin, as well as against the drugs used in second-line OS treatments that are substrates of these transporters (taxotere, etoposide, vinorelbine). Our findings indicated that inhibiting ABCB1 and ABCC1 with CBT-1®, used in association with conventional chemotherapeutic drugs, may become an interesting new therapeutic option for unresponsive or relapsed OS patients.
ABC transporters, chemosensitization, chemotherapy, drug resistance, osteosarcoma, tailored treatments.
Pharmacogenomics and Pharmacogenetics Research Unit, Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Via di Barbiano 1/10, I-40136 Bologna, Italy.