Background/aim: Synovial sarcoma (SS) is a recalcitrant neoplasm with low chemosensitivity. We recently reported that recombinant methioninase (rMETase) inhibited SS growth in a patient-derived orthotopic xenograft (PDOX) mouse model and was more effective when administered in combination with the first-line drug doxorubicin (DOX). Caffeine enhances the efficacy of anticancer drugs by overcoming drug-induced cell-cycle arrest and increasing subsequent apoptosis. Here, we determined the efficacy of oral recombinant methioninase (o-rMETase) in combined with caffeine on an SS-PDOX model.
Materials and methods: Mice bearing SS-PDOX tumors were randomized into four treatment groups of six: Untreated control; o-rMETase alone; o-rMETase with caffeine; DOX plus o-rMETase with caffeine. Tumor size and body weight were measured during the treatment and plasma L-methionine (MET) levels were measured at the end of treatment.
Results: All treatments significantly inhibited SS-PDOX tumor growth. Combining caffeine with o-rMETase was more effective than o-rMETase alone. DOX combined with o-rMETase and caffeine led to regression of SS-PDOX. Plasma MET levels were reduced with o-rMETase treatment.
Conclusion: These results suggest that combining o-rMETase and caffeine along with first-line chemotherapy can be highly effective for SS and has clinical potential for this recalcitrant disease.
Keywords: PDOX; Synovial sarcoma; caffeine; doxorubicin; oral rMETase; regression.
Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.