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The effects of 2-deoxy-D-glucose and alpha-difluoromethylornithine on the growth of pancreatic cancer in vivo.

Abstract
The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), inhibits growth of some cancers. alpha-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. We and others have previously shown that DFMO inhibits cancer growth in a number of models. The present study was designed to investigate the effects of 2-DG alone and combined with DFMO on the growth of H2T hamster pancreatic ductal adenocarcinoma. Twenty-eight male Syrian golden hamsters were inoculated with 500,000 H2T cells, and then randomized into four groups of seven each: group 1 served as control; group 2 received DFMO (3% in drinking water); group 3 received 2-DG (500 mg/kg/day) intraperitoneally; group 4 received a combination of 2-DG and DFMO. Treatment began 5 days after tumor cell inoculation and continued for 28 days. At the end of the treatment period, the area of the H2T tumor was reduced 31% by DFMO compared with a 22% reduction caused by 2-DG. Tumor weight was significantly reduced (31%) by DFMO but not by 2-DG. Tumor contents of DNA, RNA, and protein were also reduced by DFMO but not 2-DG. Tumor concentration of the polyamines, putrescine and spermidine, were reduced by DFMO, but 2-DG did not alter levels of polyamines. The combination of DFMO and 2-DG caused a significantly greater reduction in tumor weight and putrescine content compared with DFMO alone.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsR Saydjari, R W Alexander, S C Barranco, C M Townsend Jr, J C Thompson
JournalPancreas (Pancreas) Vol. 4 Issue 1 Pg. 38-43 ( 1989) ISSN: 0885-3177 [Print] United States
PMID2497460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Deoxy Sugars
  • Deoxyglucose
  • Eflornithine
Topics
  • Animals
  • Cell Division (drug effects)
  • Cricetinae
  • Deoxy Sugars (pharmacology)
  • Deoxyglucose (pharmacology)
  • Eflornithine (pharmacology)
  • Male
  • Mesocricetus
  • Pancreatic Neoplasms (metabolism, pathology)
  • Tumor Cells, Cultured

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