Recombinant Oral Methioninase (o-rMETase) Combined With Oxaliplatinum Plus 5-Fluorouracil Improves Survival of Mice With Massive Colon-Cancer Peritoneal Carcinomatosis

Abstract

Background/Aim: The present study aimed to determine if oral methioninase (o-rMETase) combined with oxaliplatinum (OXA) plus 5-fluorouracil (5-FU) increases survival of mice with peritoneal-carcinomatosis formed from HCT-116 green fluorescent protein (GFP)-expressing colon-cancer cells implanted intra-peritoneally in nude mice. Materials and Methods: HCT-116-GFP human colon-cancer cells (2×106) were injected intraperitoneally in athymic nude mice. Forty-five HCT-116-GFP colon-cancer peritoneal-carcinomatosis nude-mouse models were divided into the following groups: untreated control; combination of 5-FU (50 mg/kg, once a week), plus OXA (6 mg/kg, once a week); combination of 5-FU + OXA + o-rMETase (100 unit/day). Tumor growth was followed weekly using non-invasive GFP imaging for 3 weeks. At necropsy, tumor tissue was obtained. Frozen sections were made for fluorescence imaging. Tumor tissues were also stained with hematoxylin and eosin. The date of death of all mice was recorded. Results: o-rMETase combined with 5-FU + OXA significantly reduced peritoneal growth of the HCT-116 tumor compared to the untreated control or the combination 5-FU and OXA group. Histological analysis revealed extensive necrosis induced by the o-rMETase + 5-FU + OXA combination. The combination of 5-FU plus OXA and o-rMETase achieved significantly longer survival of the mice with peritoneal carcinomatosis compared to the control or combination of 5-FU plus OXA treatments. Conclusion: o-rMETase shows future clinical promise for increasing the survival of patients with peritoneal metastasis of colon cancer when combined with first-line treatment of this recalcitrant disease.