Efficacy of oral recombinant methioninase combined with oxaliplatinum and 5-fluorouracil on primary colon cancer in a patient-derived orthotopic xenograft mouse model

Biochem Biophys Res Commun. 2019 Oct 15;518(2):306-310. doi: 10.1016/j.bbrc.2019.08.051. Epub 2019 Aug 14.

Abstract

The aim of this study was to determine the efficacy of oral recombinant methioninase (o-rMETase) on a colon cancer primary tumor using a patient-derived orthotopic xenograft (PDOX) nude mouse model. Forty colon cancer primary tumor PDOX mouse models were divided into 4 groups of 10 mice each (total 40 mice) by measuring the tumor size. The groups were as follows: untreated control; 5-fluorouracil (5-FU) (50 mg/kg, once a week for two weeks, N = 10 mice) and oxaliplatinum (OXA) (6 mg/kg, once a week for two weeks, N = 10 mice); o-rMETase (100 units/day, oral 14 consecutive days, N = 10 mice); combination of 5-FU + OXA and o-rMETase (N = 10 mice). All treatments inhibited tumor growth compared to the untreated control. The combination of 5-FU + OXA and o-rMETase was significantly more efficacious than other treatments. The present study demonstrates the efficacy of o-rMETase combination therapy on a PDOX colon cancer primary tumor, suggesting potential clinical development of o-rMETase in recalcitrant cancer.

Keywords: Colon cancer; Methioninase; Patient-derived orthotopic xenograft; Primary tumor; Red fluorescent protein.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carbon-Sulfur Lyases / administration & dosage
  • Carbon-Sulfur Lyases / therapeutic use*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use*
  • Humans
  • Mice
  • Mice, Nude
  • Mice, Transgenic
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Recombinant Proteins
  • Carbon-Sulfur Lyases
  • L-methionine gamma-lyase
  • Fluorouracil