Fokidis H Bobby, Yieng Chin Mei, Ho Victor W, Adomat Hans H, Soma Kiran K, Fazli Ladan, Nip Ka Mun, Cox Michael, Krystal Gerald, Zoubeidi Amina, Tomlinson Guns Emma S
Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6H-3Z6, Canada; Department of Psychology, University of British Columbia, Vancouver, British Columbia V6T-1Z4, Canada.
Vancouver Prostate Centre, Vancouver, British Columbia, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia V6H-3Z6, Canada.
J Steroid Biochem Mol Biol. 2015 Jun;150:35-45. doi: 10.1016/j.jsbmb.2015.03.006. Epub 2015 Mar 19.
Dietary factors continue to preside as dominant influences in prostate cancer prevalence and progression-free survival following primary treatment. We investigated the influence of a low carbohydrate diet, compared to a typical Western diet, on prostate cancer (PCa) tumor growth in vivo. LNCaP xenograft tumor growth was studied in both intact and castrated mice, representing a more advanced castration resistant PCa (CRPC). No differences in LNCaP tumor progression (total tumor volume) with diet was observed for intact mice (P = 0.471) however, castrated mice on the Low Carb diet saw a statistically significant reduction in tumor growth rate compared with Western diet fed mice (P = 0.017). No correlation with serum PSA was observed. Steroid profiles, alongside serum cholesterol and cholesteryl ester levels, were significantly altered by both diet and castration. Specifically, DHT concentration with the Low Carb diet was 58% that of the CRPC-bearing mice on the Western diet. Enzymes in the steroidogenesis pathway were directly impacted and tumors isolated from intact mice on the Low Carb diet had higher AKR1C3 protein levels and lower HSD17B2 protein levels than intact mice on the Western diet (ARK1C3: P = 0.074; HSD17B2: P = 0.091, with α = 0.1). In contrast, CRPC tumors from mice on Low Carb diets had higher concentrations of both HSD17B2 (P = 0.016) and SRD5A1 (P = 0.058 with α = 0.1) enzymes. There was no correlation between tumor growth in castrated mice for Low Carb diet versus Western diet and (a) serum insulin (b) GH serum levels (c) insulin receptor (IR) or (d) IGF-1R in tumor tissue. Intact mice fed Western diet had higher serum insulin which was associated with significantly higher blood glucose and tumor tissue IR. We conclude that both diet and castration have a significant impact on the endocrinology of mice bearing LNCaP xenograft tumors. The observed effects of diet on cholesterol and steroid regulation impact tumor tissue DHT specifically and are likely to be mechanistic drivers behind the observed tumor growth suppression.
饮食因素在前列腺癌的患病率以及初次治疗后的无进展生存期方面仍然是主要的影响因素。我们研究了与典型西方饮食相比，低碳水化合物饮食对体内前列腺癌（PCa）肿瘤生长的影响。在完整和去势小鼠中研究了LNCaP异种移植肿瘤的生长情况，这代表了更晚期的去势抵抗性PCa（CRPC）。对于完整小鼠，未观察到饮食对LNCaP肿瘤进展（肿瘤总体积）有差异（P = 0.471），然而，与喂食西方饮食的小鼠相比，食用低碳水化合物饮食的去势小鼠的肿瘤生长速率在统计学上有显著降低（P = 0.017）。未观察到与血清PSA有相关性。饮食和去势均显著改变了类固醇谱以及血清胆固醇和胆固醇酯水平。具体而言，低碳水化合物饮食组的双氢睾酮（DHT）浓度是喂食西方饮食的荷CRPC小鼠的58%。类固醇生成途径中的酶受到直接影响，与喂食西方饮食的完整小鼠相比，从食用低碳水化合物饮食的完整小鼠分离出的肿瘤具有更高的AKR1C3蛋白水平和更低的HSD17B2蛋白水平（ARK1C3：P = 0.074；HSD17B2：P = 0.091，α = 0.1）。相比之下，来自食用低碳水化合物饮食小鼠的CRPC肿瘤中HSD17B2（P = 0.016）和SRD5A1（α = 0.1时P = 0.058）这两种酶的浓度更高。对于食用低碳水化合物饮食与西方饮食的去势小鼠，肿瘤生长与（a）血清胰岛素、（b）血清生长激素水平、（c）胰岛素受体（IR）或（d）肿瘤组织中的胰岛素样生长因子-1受体（IGF-1R）之间均无相关性。喂食西方饮食的完整小鼠血清胰岛素水平较高，这与显著更高的血糖和肿瘤组织IR相关。我们得出结论，饮食和去势对荷LNCaP异种移植肿瘤小鼠的内分泌学有显著影响。观察到的饮食对胆固醇和类固醇调节的影响尤其影响肿瘤组织中的DHT，并且可能是观察到的肿瘤生长抑制背后的机制驱动因素。
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