ISPO

Metformin clearly inhibits pancreatic cancer

M.B.Schneider MD, J. Standop MD, H. Matsuzaki MD, J. Haorah MD, A. Ulrich MD, and P.M. Pour MD.

Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE.

Aim: Our previous study has shown that in the hamster pancreatic cancer model most adenocarcinoma derive from within islets, most probably from stem cells. Stimulation of islet cell proliferation promotes but their destruction inhibits carcinogenesis. The results of our study have also suggested that the known promotional effect of a high fat (HF) diet, which in hamsters induces peripheral insulin resistance, is related to a compensatory activity, and possibly proliferation, of islet cells. The present study was to examine this possibility and investigate whether the prevention of islet cell proliferation if any, can inhibit the promotional effect of HF in pancreatic cancer induction. Methods: In a pilot study, the effect of HF diet with or without Metformin, which is known to normalize peripheral insulin resistance, on plasma insulin level and DNA synthesis of islet cells was investigated. Based on the results, in the subsequent carcinogenicity experiments two groups of HF-fed hamsters were used. One group received Metformin in drinking water for life (HF-Met group), while the other group served as a control (HF group). At the time when normalization of plasma insulin level was expected, all hamsters were treated with the pancreatic carcinogen, BOP, and the experiment was terminated 42 weeks after BOP treatment. Results: HF diet increased plasma insulin level and the rate of islet cell proliferation significantly, whereas Metformin normalized the plasma insulin level and the rate of islet cell proliferation. While 50% of hamsters in the HF group developed adenocarcinoma, none was found in the HF-Met group (p<0.05). Also significantly more hyperplastic and premalignant lesions, most of which were found within the islets, were detected in the HF group. Remarkably, Metformin also inhibited the induction of ductal lesions. Conclusion: The results lend further support on the significant role of islet cells in pancreatic carcinogenesis and may explain the association between pancreatic cancer and obesity, which is usually associated with peripheral insulin resistance.

For more information, contact jstandop@unmc.edu

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Dietary Influences.

http://www.cancerprev.org/Journal/Issues/26/101/1096/4412