The Effection Of Ketogenic Diet With Different Kinds Of Fatty Acids On The Growth Of Human Cancer Cells In Nude Mice

Objection:The ketogenic diet is high in fat content and low in carbohydrate and protein content. Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, β-hydroxybutyrate dehydrogenase (β-OHBDH) and succinyl-CoA:3-ketoacid CoA transferase (SCOT). The deficiencies in these enzymes are important for tumor management when glucose is not sufficient and when cells would require ketone bodies for energy. This may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet. In this study, human colon cancer cells were transplanted subcutaneously into nude mice in order to observe the impact of the ketogenic diets with different kinds of fatty acids on tumor growth and to find out the possible mechanism of the anti-cancer function of ketogenic diet.Methods:Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of600mm3to700mm3. The three diets were compared based on tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume).Results:The tumor growth in the MKD and LKD groups were significantly delayed compared to that in the SD group. Tumors in the MKD, LKD and SD group reached the target tumor volume at35.1±7.6days,33.8±6.7days and24.8±3.1days, while the median time of tumor palpability in SD, MKD and LKD groups are6,8and8days, respectively. The ketone body, total cholesterol (TCHO) and high-density lipoprotein cholesterol (HDL-c) together with low-density lipoprotein cholesterol (LDL-c) in both MKD and LKD groups were elevated with a slight reduce in serum insulin compared to the SD group, and the difference in serum glucose and triglycerides(TG) were not significant. Importantly, they revealed significantly larger necrotic areas and less vessel density than tumors of the SD group.Conclusions:Application of an unrestricted ketogenic diet enriched with omega-3fatty acids and MCT or lard only delayed tumor growth in a mouse xenograft model. Although the difference between MKD and LKD group is not significant, there is a tendency that MKD is more efficient. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant functions such as invasive growth and metastasis.