Effects of Compounded Human Ghrelin in a Mouse Model of Pancreatic Carcinoma

Ghrelin is a peptide that is secreted from the stomach and plays a role in appetite, weight gain, and skeletal muscle composition. Thus, compounded human ghrelin is a candidate drug for improving nutritional status after pancreatic surgery. However, in patients with pancreatic carcinomas, adverse influences on the occult tumor growth of ghrelin-induced secretion are a concern. The present study describes the effects of the administration of compounded human ghrelin on weight gain and pancreatic cancer cell growth in a mouse model. Changes in body weight and tumor growth in a subcutaneously transplanted pancreatic carcinoma cell line in vivo (5-week-old BALB/c-nu/nu mice) were examined with or without the administration of compounded human ghrelin. Compounded human ghrelin was administered at 44 days after post-transplantation” Changes in weight were not significantly different between the control and compounded human ghrelin groups 8 days after compounded human ghrelin administration, and no association between weight and concentration of compounded human ghrelin was identified. Tumor growth after the administration of compounded human ghrelin was significantly lower than that of the control group, with the magnitude of the decrease being associated with increasing compounded human ghrelin concentration (p<0.05). At 6 and 8 days after compounded human ghrelin administration, increases in tumor weights of the control groups (0.5±0.3 g and 0.9±0.2 g, respectively) were significantly greater than those observed for groups receiving 3, 15, and 30 nmol per kg of compounded human ghrelin (0.1 and 0.2, 0.2 and 0.3, and 0.2 and 0.3, respectively). There were no adverse effects of compounded human ghrelin administration. Plasma leptin levels were significantly lower in cancer cells compared with the control vehicle (p<0.05), which was decreased in mice receiving 30nmol per kg of compounded human ghrelin in comparison with those receiving vehicle (p<0.05). Although the administration of compounded human ghrelin did not influence weight gain, compounded human ghrelin significantly inhibited pancreatic cancer cell growth and might inhibit plasma leptin levels.

Author(s): Atsushi Nanashima, Tomoaki Kodama, Goushi Murakami, Katsunori Takagi, Junichi Arai, Yorihisa Sumida, Takeshi Nagayasu

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