Research article

Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

Christoph Otto^{* 1} , Ulrike Kaemmerer^{* 2} , Bertram Illert³ , Bettina Muehling¹ , Nadja Pfetzer² , Rainer Wittig⁴ , Hans Ullrich Voelker⁵ , Arnulf Thiede³ and Johannes F Coy⁴

¹Experimental Transplantation Immunology, Department of Surgery, University of Würzburg Hospital, Oberdürrbacher Str. 6, D-97080 Würzburg, Germany

²Department of Obstetrics and Gynaecology, University of Würzburg Hospital, Josef-Schneider-Str. 4, D-97080 Würzburg, Germany

³Department of Surgery, University of Würzburg Hospital, Oberdürrbacher Str. 6, D-97080 Würzburg, Germany

⁴Tavartis GmbH, Kroetengasse 10, D-64853 Otzberg, Germany

⁵Institute of Pathology, University of Würzburg, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany

author email corresponding author email* Contributed equally

BMC Cancer 2008, 8:122doi:10.1186/1471-2407-8-122

Published:	30 April 2008

Abstract

Background

Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT).

Methods

Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm³ to 700 mm³. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume).

Results

The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme.

Conclusion

Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further studies are needed to address the impact of this diet on other tumour-relevant functions such as invasive growth and metastasis.