The effect of keratinocyte growth factor on tumour growth and small intestinal mucositis after chemotherapy in the rat with breast cancer

Cancer Chemother Pharmacol. 2002 Jul;50(1):53-8. doi: 10.1007/s00280-002-0460-4. Epub 2002 May 14.

Abstract

Purpose: Mucositis from cancer chemotherapy is a common problem for which there is no definitive treatment. It produces significant morbidity and occasional mortality. Prevention and successful treatment could significantly enhance the quality of life of patients, and improve survival; however any potential preventative agent must not enhance tumour growth. The aims of this study were to assess the effect of keratinocyte growth factor (KGF) on breast tumour growth, and in preventing small intestinal mucositis induced by methotrexate (MTX).

Methods: Tumour-bearing rats received KGF or saline for 5 days prior to either MTX or saline treatment, and were killed 24 h after the last MTX injection. The weights of the tumour, small and large intestines, and liver were recorded. Apoptosis was assessed by TUNEL assay in the tumour and jejunum. Intestinal morphometry was used to assess villus area, crypt length and mitotic crypt count. Tumour proliferation was assessed by mitotic count.

Results: KGF increased the weight of the small intestine prior to chemotherapy but the weight was not maintained after chemotherapy. KGF synergized with MTX to increase apoptosis in both intestinal crypts and the breast cancer. KGF also reduced tumour size.

Conclusions: We conclude that KGF had a modest effect on intestinal growth prior to chemotherapy. It did not protect the gut from mucositis, nor did it worsen morphometry. It reduced tumour size.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Animals
  • Antimetabolites, Antineoplastic / adverse effects
  • Cell Division / drug effects
  • DNA, Neoplasm / drug effects
  • Enteritis / chemically induced
  • Enteritis / drug therapy*
  • Enteritis / pathology
  • Female
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors / therapeutic use*
  • In Situ Nick-End Labeling
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / pathology
  • Keratinocytes / metabolism
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / pathology
  • Methotrexate / adverse effects
  • Rats
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Survival Rate

Substances

  • Antimetabolites, Antineoplastic
  • DNA, Neoplasm
  • Fgf7 protein, rat
  • Recombinant Proteins
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors
  • Methotrexate