The effects of glycemic index on prostate cancer progression in a xenograft mouse model
Previously, we found low-carbohydrate diets slowed prostate cancer (PC) growth and increased survival vs. a Western diet in mice, by inhibiting the insulin/IGF-1 axis. Thus, we tested whether modifying carbohydrate quality to lower glycemic index (GI) without changing quantity results in similar benefits as with reduced quantity. Male SCID mice injected with LAPC-4 cells were single-housed and randomized when their tumors reached 200mm3 on average to a LoGI (48% carbohydrate kcal, from Hylon-VII) or HiGI Western diet (48% carbohydrate kcal, from sucrose). Body weight and tumor volume were measured weekly. Body composition was assessed 35 days after randomization. Blood glucose and serum insulin, IGF-1 and IGFBP3 were measured at study end when tumor volumes reached 800mm3. We analyzed gene expression of mice tumors by RNA-sequencing and human tumors using the Prostate Cancer Transcriptome Atlas. There were no significant differences in tumor volume (P>0.05), tumor proliferation (P=0.29), and overall survival (P=0.15) between groups. At 35 days after randomization, the LoGI group had 30% lower body fat (P=0.007) despite similar body weight (P=0.58). At sacrifice, LoGI mice had smaller livers (P<0.001) and lower glucose (P=0.15), insulin (P=0.11), IGF-1 (P=0.07) and IGF-1:IGFBP3 ratio (P=0.05), and higher IGFBP3 (P=0.09) vs. HiGI, although none of these metabolic differences reached statistical significance. We observed differential gene expression and pathway enrichment in mice tumors by diet. The most upregulated and downregulated gene in the LoGI group showed expression patterns more closely resembling expression in human benign prostate tissue vs. PC. In this single mouse xenograft model, consuming a low GI diet did not delay PC growth or survival vs. a high GI diet despite suggestions of decreased activation of the insulin/IGF-1 pathway. These data suggest that improving carbohydrate quality alone while consuming a high carbohydrate diet may not effectively slow PC growth. Overall design: We investigated the effect of carbohydrate quality on prostate cancer growth and survival in a xenograft model comparing high vs. low glycemic index Western diets. Tumors from a subset of mice (n=3/group) were used for gene expression analysis by RNA-sequencing.