Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model

• Published in: Oncotarget 2018-04, Vol.9 (27), p.19263-19272
• Main Authors: Igarashi, Kentaro, Kawaguchi, Kei, Li, Shukuan, Han, Qinghong, Tan, Yuying, Gainor, Emily, Kiyuna, Tasuku, Miyake, Kentaro, Miyake, Masuyo, Higuchi, Takashi, Oshiro, Hiromichi, Singh, Arun S, Eckardt, Mark A, Nelson, Scott D, Russell, Tara A, Dry, Sarah M, Li, Yunfeng, Yamamoto, Norio, Hayashi, Katsuhiro, Kimura, Hiroaki, Miwa, Shinji, Tsuchiya, Hiroyuki, Eilber, Fritz C, Hoffman, Robert M
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.24996

Synovial sarcoma (SS) is a recalcitrant subgroup of soft tissue sarcoma (STS). A tumor from a patient with high grade SS from a lower extremity was grown orthotopically in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) mouse model. The PDOX mice were randomized into the following groups when tumor volume reached approximately 100 mm : G1, control without treatment; G2, doxorubicin (DOX) (3 mg/kg, intraperitoneal [i.p.] injection, weekly, for 2 weeks; G3, rMETase (100 unit/mouse, i.p., daily, for 2 weeks); G4 DOX (3mg/kg), i.p. weekly, for 2 weeks) combined with rMETase (100 unit/mouse, i.p., daily, for 2 weeks). On day 14 after treatment initiation, all therapies significantly inhibited tumor growth compared to untreated control, except DOX: (DOX: = 0.48; rMETase: 0.005; DOX combined with rMETase < 0.0001). DOX combined with rMETase was significantly more effective than both DOX alone ( 0.001) and rMETase alone ( 0.05). The relative body weight on day 14 compared with day 0 did not significantly differ between any treatment group or untreated control. The results indicate that r-METase can overcome DOX-resistance in this recalcitrant disease.