The effects of 2-deoxy-d-glucose and a-difluoromethylornithine on the growth of pancreatic cancer in vivo

The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), inhibits growth of some cancers. a-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) intraperitoneal-ly; 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. These results indicate that DFMO is capable of inhibiting pancreatic cancer growth in vivo and that this inhibition is potentiated by the addition of the glucose antimetabolite 2-DG, although 2-DG alone has no antitumor effect. Further study of 2-DG and DFMO may provide information of therapeutic value.