生酮饮食对人结肠癌裸鼠皮下移植瘤生长的影响

摘要

Objective:To observe the effect of ketogenic diet on the growth of human colon cancer cells in nude mice and to de-termine its possible mechanisms. Methods:A total of 24 male BALB/C nude mice were injected subcutaneously with the tumor cells of the colon cancer cell line HCT116. These animals were randomized into two feeding groups. One group was fed with a ketogenic diet (KD group;n=12), and the other group was given a standard diet (SD group;n=12) ad libitum. Experiments were completed upon at-taining a target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on body weight, serum glucose, ketone body, insulin, tumor growth, and survival time, which is the interval between tumor cell injection and attainment of target tumor vol-ume. Results:The tumor growth was significantly more delayed in the KD group than in the SD group. Tumors in the KD and SD groups reached the target tumor volume at 33.8 ± 6.7 days and 24.8 ± 3.1 days, respectively. The ketone body in the KD group was ele-vated with a slight reduction in serum insulin, and the difference in serum glucose in the two groups was insignificant. Importantly, the KD group had significantly larger necrotic areas and less vessel density than the SD group. Conclusion:The application of an unre-stricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and its effect on other tumor-relevant functions, such as invasive growth and metastasis.%目的：观察生酮饮食对人结肠癌裸鼠皮下移植瘤生长的影响；探讨生酮饮食可能的作用机制。方法：24只雄性BALB/C裸鼠皮下注射人结肠癌HCT116细胞系后随机分成2组，分别给予正常饮食（standard diet，SD）及生酮饮食（ketogenic diet，KD），两组饮食均不限制总量。当肿瘤体积达到600～700 mm3时实验终止，并将接种当日至肿瘤达到目标体积的时间定义为肿瘤生长期。比较不同饮食对裸鼠重量、血糖、血酮体、血胰岛素水平以及肿瘤生长等的影响。结果：与SD组相比，KD组裸鼠肿瘤生长明显延缓，KD组及SD组皮下移植瘤达到目标体积的时间分别为（33.8±6.7）天和（24.8±3.1）天。KD组裸鼠血酮体水平显著升高，血胰岛素水平轻度下降，而血糖水平无明显变化，KD组肿瘤组织坏死面积明显增大，而血管密度则显著降低。结论：不限制总量的生酮饮食可明显延缓裸鼠人结肠癌细胞皮下移植瘤模型的生长。生酮饮食抗肿瘤治疗的作用机制及其对肿瘤其他特性如侵袭性和转移性等的影响有待进一步研究证实。