Oral Recombinant Methioninase Sensitizes a Bladder Cancer Orthotopic Xenograft Mouse Model to Low-dose Cisplatinum and Prevents Metastasis

• Published in: Anticancer research Vol. 40; no. 11; pp. 6083 - 6091
• Main Authors: SUN, YU, NISHINO, HIROTO, SUGISAWA, NORIHIKO, YAMAMOTO, JUN, HAMADA, KAZUYUKI, ZHU, GUANGWEI, LIM, HYE IN, HOFFMAN, ROBERT M.
• Format: Journal Article
• Language: English
• Published: Athens International Institute of Anticancer Research 01.11.2020
• Subjects: Bladder; Bladder cancer; Body weight; Cancer; Cell proliferation; Dosage; Fluorescence; Green fluorescent protein; Immunohistochemistry; Metastases; Metastasis; Tumors; Xenografts; Xenotransplantation
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14629

Background/Aim: The aim of the study was to determine if oral recombinant methioninase (o-rMETase) can sensitize an orthotopic bladder tumor in nude mice to low-dose cisplatinum (CDDP). Materials and Methods: The green fluorescent protein (GFP)-expressing UM-UC-3-GFP bladder cancer was surgically orthotopically implanted (SOI) to the bladder in nude mice. The treatment was initiated when the primary tumor volume reached 100 mm3. Mice were assigned to 3 groups: G1: Saline vehicle (0.1 ml per mouse, oral, twice per day); G2: low-dose CDDP (0.5 mg/kg, intraperitoneal twice per week); G3: o-rMETase + low-dose CDDP (100 units per mouse, oral, twice per day + 0.5 mg/kg, intraperitoneal twice per week, respectively). Tumor volume and body weight were measured twice per week. The expression of Ki-67 was detected by immunohistochemistry to evaluate cell proliferation. Results: The combination of o-rMETase and low-dose CDDP increased inhibition efficacy compared to low-dose CDDP monotherapy, on primary-tumor growth (p=0.032) and metastasis (p=0.002). Conclusion: The combination of o-rMETase with low-dose CDDP has future clinical potential for bladder cancer.