PP56 improves energy homeostasis in a mouse model of pancreatic cancer.
In this study, we investigated whether the anti-inflammatory drug PP56 (alpha-trinositol) may improve cancer-induced metabolic disorders. We implanted human MiaPaCa2 pancreatic cancer cells in the pancreas of 14 athymic mice for 12 weeks, using six intact littermates as normal controls. During the 12 weeks, seven tumor-cell recipients were treated with PP56 by daily injection (PPT mice). The tumor-cell recipients that were otherwise untreated were used as tumor controls (TC mice). Impaired glucose tolerance and decreased body weight gain were seen in TC but not PPT mice. When an enzyme for fatty acid beta-oxidation namely medium-chain acyl-CoA dehydrogenase (MCAD) was determined in tumor grafts; tumors from PPT mice showed more MCAD than those from TC mice. This suggests that PP56 stimulated fatty acid beta-oxidation in MiaPaCa2 cells in vivo. In keeping with this notion, PPT mice had decreased plasma free fatty acids. In vitro, we demonstrated that MiaPaCa2 cells consumed more fatty acids in the presence of PP56. In another experiment, we infused PP56 or vehicle in normal mice and found that PP56 decreased circulating glucose in the animals. We also showed that PP56 increased glucose transport in L6 skeletal muscle cells in vitro. In conclusion, PP56 increases the turnover of circulating nutrients such as glucose and helps maintain energy homeostasis in mice with pancreatic cancer.
Wang
Feng
F
Department of Clinical Science, Intervention and Technology, Division of Surgery, Karolinska University Hospital, Huddinge, Sweden. feng.wang@ki.se
Larsson
Jörgen
J
Herrington
Margery K
MK
Permert
Johan
J
D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007295:Inositol Phosphates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D005227:Fatty Acids; D007295:Inositol Phosphates; D042964:Acyl-CoA Dehydrogenase; C059368:atrinositol