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Updated: Jul 8, 2025
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
The effects of glycemic index on prostate cancer progression in a xenograft mouse model
Gloria Cecilia Galván1, Everardo Macias2, Sergio Sanders1
1Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Background:
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.
Methods:
Male SCID mice injected with LAPC-4 cells were single-housed and randomized when their tumors reached 200 mm3 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 800 mm3. We analyzed gene expression of mice tumors by RNA-sequencing and human tumors using the Prostate Cancer Transcriptome Atlas.
Results:
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.
Conclusions:
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.
Insights
A low glycemic index (GI) diet did not slow prostate cancer (PC) growth or improve survival in mice compared to a high GI diet. Modifying carbohydrate quality alone may not be sufficient to inhibit PC progression.
Area of Science:
- Oncology
- Metabolic Research
- Nutritional Science
Background:
- Previous studies indicated low-carbohydrate diets inhibit prostate cancer (PC) growth and enhance survival in mice by affecting the insulin/IGF-1 axis.
- This study investigated if altering carbohydrate quality to a lower glycemic index (GI), without changing the quantity, offers similar benefits to carbohydrate reduction.
Purpose of the Study:
- To determine if a low-GI diet, compared to a high-GI diet, impacts prostate cancer growth, survival, and related metabolic pathways in a mouse model.
- To assess the effects of dietary carbohydrate quality on body composition, organ weights, and key metabolic markers including insulin and IGF-1.
Main Methods:
- Male SCID mice bearing LAPC-4 human PC xenografts were fed either a low-GI (Hylon-VII) or high-GI (sucrose) Western diet (48% carbohydrate kcal).
- Tumor volume, body weight, body composition, and survival were monitored. Blood glucose, insulin, IGF-1, and IGFBP3 levels were measured at study termination.
- Tumor gene expression was analyzed via RNA-sequencing in mice and compared to human prostate cancer data.
Main Results:
- No significant differences were observed in tumor volume, proliferation, or overall survival between the low-GI and high-GI diet groups.
- The low-GI group exhibited significantly lower body fat (30%) and smaller livers, despite similar body weight.
- While trends suggested lower glucose, insulin, IGF-1, and a lower IGF-1:IGFBP3 ratio in the low-GI group, these did not reach statistical significance. Gene expression analysis revealed patterns in low-GI tumors resembling benign prostate tissue.
Conclusions:
- In this mouse xenograft model, a low-GI diet did not impede prostate cancer progression or survival compared to a high-GI diet.
- The findings suggest that improving carbohydrate quality alone, within a high-carbohydrate diet, may not be sufficient to inhibit the insulin/IGF-1 pathway and slow PC growth.
