International Journal of Colorectal Disease

, Volume 21, Issue 7, pp 625–631

5-Fluorouracil (5FU) treatment does not influence invasion and metastasis in microsatellite unstable (MSI-H) colorectal cancer

  • Janindra Warusavitarne
  • Palaniappan Ramanathan
  • Anthony Kaufman
  • Bruce G. Robinson
  • Margaret Schnitzler
Original Article

Abstract

Microsatellite instability is a recognised pathway of colorectal carcinogenesis responsible for about 15% of all sporadic colorectal cancers. Recent evidence has suggested that these tumours may not have the same response as microsatellite stable colon cancers to 5-fluorouracil (5FU)-based chemotherapy. The response to 5FU in four microsatellite unstable (MSI-H) cell lines was examined by cell viability assays and invasion assays. Flow cytometry was used to assess the effect of 5FU on MSI-H cell lines. In vivo response to 5FU was assessed by intraperitoneal injection of 5FU or control to 80 nude mice that had received intrasplenic injections of an MSI-H cell line KM12C prior to commencing treatment. There was inhibition of cell growth in MSI-H cell lines when treated with 5FU. There was no difference in invasiveness in the MSI-H cell lines when treated with 5FU. Primary tumours formed in 27 of the untreated and 25 of the 5FU treated mice (p=NS). There was a 36% reduction in splenic weight in those mice treated with 5FU (p<0.03). Metastases formed in 5 of the untreated and 9 of the treated mice (p=0.12). 5FU treatment of MSI-H tumours results in a reduction in growth but does not result in a reduction in invasion or metastasis.

Keywords

Colorectal cancer Microsatellite instability (MSI-H) Chemotherapy 5-Fluorouracil (5FU) Metastasis 

Abbreviations

5FU

5-Fluorouracil

MSI

Microsatellite unstable

MSI-H

High-frequency microsatellite unstable

MSS

Microsatellite stable

PBS

Phosphate-buffered saline

BrDU

Bromodeoxyuridine

FITC

Fluorescein

TS

Thymidine synthetase

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Janindra Warusavitarne
    • 1
  • Palaniappan Ramanathan
    • 1
  • Anthony Kaufman
    • 2
  • Bruce G. Robinson
    • 1
  • Margaret Schnitzler
    • 1
  1. 1.Department of Cancer Genetics, Kolling Institute of Medical ResearchRoyal North Shore Hospital and University of SydneySt. LeonardsAustralia
  2. 2.Department of Anatomical PathologyPalms, Royal North Shore HospitalSt. LeonardsAustralia

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