Oral recombinant methioninase combined with oxaliplatinum and 5-fluorouracil regressed a colon cancer growing on the peritoneal surface in a patient-derived orthotopic xenograft mouse model

Jun Ho Park, Qinghong Han, Ming Zhao, Yuying Tan, Takashi Higuchi, Sang Nam Yoon, Norihiko Sugisawa, Jun Yamamoto, Michael Bouvet, Bryan Clary, Shree Ram Singh, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The aim of this study was to determine the efficacy of oral recombinant methioninase (o-rMETase) on a model of colon cancer growing on the peritoneal surface using a patients-derived orthotopic xenograft (PDOX) nude mouse model. Forty PDOX mouse models with colon cancer growing on the peritoneum were divided into 4 groups of 10 mice each by measuring the tumor size and fluorescence intensity: untreated control; 5-fluorouracil (5-FU) (50 mg/kg, once a week for two weeks, ip) and oxaliplatinum (OXA) (6 mg/kg, once a week for two weeks, ip); o-rMETase (100 units/day, oral 14 consecutive days); combination 5-FU + OXA and o-rMETase. All treatments inhibited tumor growth compared to the untreated control. The combination of 5-FU + OXA plus o-rMETase was significantly more efficacious than the control and each drug alone and was the only treatment that caused tumor regression. The present study is the first demonstrating the efficacy of o-rMETase combination therapy on a PDOX model of peritoneal colon cancer, suggesting potential clinical development of o-rMETase in a recalcitrant cancer.

Original languageEnglish
Pages (from-to)109-114
Number of pages6
JournalTissue and Cell
Volume61
DOIs
Publication statusPublished - 2019 Dec
Externally publishedYes

Keywords

  • Colon cancer
  • Methioninase
  • Nude mouse
  • Orthotopic
  • Patient-derived
  • Red fluorescent protein
  • Xenograft

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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