The effects of ketogenic diet on the growth of human lung carcinoma xenograft in nude mice

TIAN Yan; XIAN Le-wu

doi:10.3969/j.issn.1001-9448.2018.05.006

Abstract：Objective To study the effects of ketogenic diet on the growth of human lung carcinoma xenograft in nude mice, and to explore its related mechanism. Methods A total of 24 male BALB/C nude mice were subcutaneously injected with the lung tumor cells for establishment of transplantation Tumor Model. These nude mice were randomized into two feeding groups. One group was fed with ketogenic diet (Group KD, n = 12), and the other group was given with standard diet (Group SD, n = 12). The growth of body weight and the subcutaneous transplanted tumor were observed. The blood glucose, blood insulin, blood ketone body were recorded. The expression of Ki-67, MMP9, VEGF, IGF-1 miR-451 and miR-210 of subcutaneous transplantation tumor tissue was measured by reverse transcription polymerase chain reaction (RT-PCR). The expression of AMPK protein and mTOR protein of subcutaneous transplantation tumor tissue was measured by Western blot. Results There was no significant difference in nude mice weight between the two groups (P ＞ 0. 05). The blood glucose level of Group KD group lightly decreased (P ＞ 0. 05), while blood ketone was significantly reduced when compared with Group SD (P ＜ 0. 05). In Group SD, the diameter of transplanted tumor was significantly larger than that in Group KD (0. 86 ± 0. 07 cm vs. 0. 69 ± 0. 07 cm, P ＜ 0. 05). The expression levels of Ki 67, MMP9, VEGF and IGF-1 mRNA in Group KD was higher than those in Group KD. The expression of miR-451 and miR-210 in transplanted tumor tissue of Group SD was higher than that of Group KD. The expression of AMPK protein in Group SD group was significantly lower than that in Group KD group, while the expression of mTOR protein in Group SD group was significantly higher than that in Group KD (P ＜ 0. 05). Conclusion The application of ketogenic diet can inhibit tumor growth in mouse lung carcinoma xenograft model. The anticancer mechanism of ketogenic diet may be via affecting the AMPK/mTOR signaling pathway, and further regulating the expression of Ki-67, MMP9, VEGF, IGF-1 miR-451 and miR-210 in cancer cells.