Table 1.
Summary of preclinical models on dietary-fat induced prostate cancer development and progression.
| Authors | Years | Animal Models | Tumors | Diet Summary | End Point | Summary of the Results |
|---|---|---|---|---|---|---|
| Wang [11] | 1995 | Nude mice | LNCaP | 40.5%, 30.8%, 21.2%, 11.6%, or 2.3l% fat | Tumor growth rates, tumor weights, ratios of final tumor weights to animal weights, PSA | Groups that continued to receive a 40.5l% fat diet were substantially greater tumor growth rates, final tumor weights, and ratios of final tumor weights to animal weights than those whose diets were changed to 2.3 kcal%, 11.6 kcal%, or 21.2 kcal% fat. |
| Connoly [12] | 1997 | Nude mice | a) DU145 subcutaneous xenograft, b) DU145 into prostate | a) 18:2 ω-6-rich vs. 18:3 ω-3-rich vs. 20:5 and 22:6 ω-3-rich, b) ω-6-rich vs. a LF | Tumor growth | a) 18:2 ω-6-rich vs. 18:3 ω-3-rich mice were similar; a 30% reduction in tumor growth was observed in the 20:5 and 22:6 ω-3-rich groups. b) The mean tumor weight in the ω-6-rich group was twice that in the low-fat group. |
| Ngo [13] | 2002 | LNCaP cultured with human serum | Before and after residential diet and exercise | Cell growth, apoptosis, necrosis | Serum-stimulated LNCaP cell growth was reduced by 30% in post-11-day serum and by 44% in long-term serum relative to baseline. LNCaP cells incubated with post-diet and exercise serum showed higher apoptosis/necrosis, compared to baseline. | |
| Barnard [14] | 2003 | LNCaP cultured with human serum | Volunteer serum (control, LF and exercise, exercise alone) | Cell growth | Both the LF/exercise and exercise alone groups had reduced LNCaP cell growth compared to control. | |
| Ngo [15] | 2003 | CB17 SCID | a) LAPC-4 xenograft, b) LAPC-4 culture with 10% mouse serum | HFD (42%) vs. LFD (12%) | a) tumor growth, PSA, b) cell growth | LFD mice had significantly slower tumor growth rates and lower serum PSA levels compared to HFD mice. LAPC-4 cells cultured in vitro with media containing serum from LFD mice demonstrated slower growth than LAPC-4 cells cultured in media containing HFD mice serum. |
| Ngo [16] | 2004 | CB17 SCID | LAPC-4 xeograft | HFD (42%) vs LFD (12%) | Tumor growth, survival | Tumor latency and mouse survival were significantly longer in the LFD castration versus HFD castration group. |
| Venkateswaran [17] | 2007 | Swiss nu/nu | LNCaP xenograft | HC + HFD vs. LC + HFD | Tumor growth | Mice on the HC–HFD diet experienced increased tumor growth. |
| Berquin [18] | 2007 | Prostate-specific Pten deletion mouse | High ω-6 vs. ω-3 diet | Prostate weight, rate of invasive carcinoma | Prostate weight was significantly lower in mice fed high ω-3; half of the mice fed ω-3 develop invasive carcinoma, whereas 80% of the mice fed high ω-6 diet had invasive carcinoma. | |
| Kobayashi [19] | 2008 | Prostate specific High-Myc transgenic mouse | a)LNCaP, b)MycCap with mice serum | HFD (42%) vs LFD (12%) | Rate of mPIN and cancer incidence | The number of mice that developed invasive adenocarcinoma at 7 months was 27 % less in the LFD group (12/28) compared to the HFD group (23/33, p = 0.04). Epithelial cells in PIN lesions in the LFD group had a significantly lower proliferative index compared to epithelial cells in the HFD group (21.7% vs. 28.9%, p < 0.05). |
| Freedland [20] | 2008 | SCID | LAPC-4 xenograft | NCKD (84% fat) vs. LFD (12% fat) vs. WD (40% fat) | Tumor growth, survival | NCKD mice tumor volumes were 33% smaller than WD mice (rank-sum, p = 0.009). No differences in tumor volume were observed between LFD and NCKD mice with the latter having the longest survival. |
| Narita [16] | 2008 | BALB/c-nu/nu | LNCap xenograft | HF (56.7%) vs. LF (10.2%) | Tumor volume, PSA | Tumor volume and serum PSA levels were significantly higher in the HFD group than in the LFD group. |
| Mavropoulos [21] | 2009 | SCID | LNCaP xenograft | NCKD (83% fat) vs. LFD (12% fat) vs. WD (40% fat) | Tumor growth, survival | Tumor volumes in the WD group remained significantly larger than tumor volumes in the LFD and NCKD groups. Survival was significantly prolonged for the LF (hazard ratio, 0.49; 95% confidence interval, 0.29–0.79; p = 0.004) and NCKD groups (hazard ratio, 0.59; 95% confidence interval, 0.37–0.93; p = 0.02). |
| Tamura [22] | 2009 | Nude mice | LNCaP xenograft | HFD (14%) vs LFD (6%) | Tumor growth | LNCaP-Mock cells did not reveal any significantgrowth promotion by breeding with HFD. HFD breeding significantly promoted the growth of LNCaP-ELOVL7-1 cells in vivo (p = 0.0081). |
| Kalaany [23] | 2009 | Prostate-specific Pten deletion mouse | Ad libitum vs. CR | Percentage of proliferation and apoptosis | CR did not affect a PTEN-null mouse model of prostate cancer but significantly decreased tumor burden in a mouse model of lung cancer lacking constitutive PI3K signaling. | |
| Bushemeyer [24] | 2010 | SCID | LAPC-4 xenograft | 7 types of diet | Tumor growth, survival | No significant differences in tumor volume were observed among the various groups at any time point. Overall, the treatment group was not significantly related to survival. |
| Llaverias [25] | 2010 | TRAMP mouse | WD (21.2%) vs. chow (4.5%) | Prostate tumor incidence and progression | TRAMP mice fed a WD were shown to develop larger tumors compared to mice fed a chow diet. 67% (6 of 9 mice) of TRAMP mice fed a WD exhibited at least one metastatic focus, whereas 43% (3 of 7 mice) of mice fed a chow diet exhibited the same. | |
| Lloyd [26] | 2010 | SCID | LAPC-4 xenograft | WD (40%) vs. chow (12%) | Tumor growth, survival | No difference in tumor growth or survival between chow and WD was observed. |
| Aronson [27] | 2010 | LNCaP cultured with human serum | PCa men with LF, high-fiber, soy protein-supplemented diet or WD for 4 weeks | Cell growth | LF, high-fiber, soy protein-supplement diet decreased LNCaP cancer cell growth. | |
| Masko [28] | 2010 | SCID CB17 | LAPC-4 xenograft | NCKD (84% fat), 10% carbohydrate diet (74% fat), or 20% carbohydrate diet (64% fat). | Tumor volume, PSA, survival | Tumors were significantly larger in the 10% carbohydrate group on days 52 and 59 (p < 0.05) and at no other point during the study. Diet did not affect survival (p = 0.34). |
| Akinsete [29] | 2012 | C3 (1) Tag transgenic mouse | High ω-6 vs. ω-3 diet | Tumor progression, apoptosis | Slower progression of tumorigenesis and enhanced apoptosis was observed in dorsalateral prostate of high ω-3 diet mice than in high ω-6 diet mice. | |
| Mao [30] | 2012 | Homozygous prostate-specific RXRα knockout mouse | NWD (higher fat content, reduced calcium, vitamin D, and fiber) or AIN-76A | A significant joint effect of NWD and RXRα status in developing mPIN, but interaction was not significant owing to the small sample size. | ||
| Bonorden [31] | 2012 | a) TRAMP mouse, b) C57/BL6 | b) TRAMP-C2 allograft | LFD (AIN-93M) vs. AIN-93M-HFD (33%) | a) tumor differentiation, percentage of metastasis, b) tumor weight and volume | No difference in the prostates of TRAMP mice. TRAMP-C2 cells grew faster when the mice were fed a HFD. |
| Konijeti [32] | 2012 | SCID | 22Rv1 | HFD (43.3%) + saline, HFD + IGF-1R-Ab, LFD (12.4%) + saline, LFD + IGF-1R-Ab | Tumor volume | No significant differences in final tumor volumes or final tumor weights were observed between the treatment groups. At day 14 of the intervention, the mean tumor volume was significantly lower in the LFD + IGF-1R-Ab group than in the HF group. |
| Huang [33] | 2012 | BALB/c-nu/nu | LNCaP xenograft | HFD (59.9%) vs. HCD (9.5%) vs CD (41.2%) | Tumor volume | The tumor growth of LNCaP xenograft was significantly higher in the HFD group than in the HCD and CD groups. |
| Wang [34] | 2012 | a) nude mice, b) Prostate-specific Pten deletion mouse | a) pten-/- allograft | High ω-6 vs ω-3 diet | a) tumor volume and weight, b) body weight, invasion rate, Ki67 | ω-3 PUFA resulted in slower growth of castration-resistant tumors compared to ω-6 PUFA. |
| Vandelsluis [35] | 2013 | Nu/nu athymic mice | LNCaP xenograft | HFD (23.8%) vs. SD (6.0%) | Tumor volume | The HF with exercise group showed significantly higher tumor growth rates compared to all other groups. The SD with exercise group had significantly lower tumor growth rates of compared to the HFD without exercise group. |
| Pommier [36] | 2013 | C57BL/6 Lxra and Lxrb double knockout mice | Normal or hypercholesterolemic diet | Presence of PIN, number of Ki-67 positive cells | High-cholesterol diet induced proliferation in LXR mutant mouse prostate. | |
| Huang [37] | 2014 | BALB/c-nu/nu | LNCaP xenograft | HFD (59.9%) vs. LFD (9.5%) | Tumor volume | The tumor growth of LNCaP xenograft was significantly higher in the HFD group than the LFD groups. |
| Moiola [38] | 2014 | Swiss nu/nu | PC-3 xenograft | HFD (homemade) vs. CD | Tumor volume | No significant differences in tumor growth were observed in CD-fed mice; however, we found that only 60% of HFD-fed mice inoculated with CtBP1-depleted cells developed a tumor. |
| Chang [39] | 2014 | TRAMP mouse | HFD (45%) vs. CD (10%) | Histophathologica score | Histopathological scores in the dorsal and lateral lobes were higher in the 10-week HFD group than in the 10-week CD group. | |
| Liu [40] | 2015 | Pten haploinsufficientmale mice | High calorie vs. regular diet | mPIN score | High-calorie diet caused neoplastic progression, angiogenesis, inflammation, and epithelial-mesenchymal transition | |
| Cho [41] | 2015 | a) TRAMP, b) C57BL/6J | b) TRAMPC2 allograft | HFD (60%) vs. CD (10%) | Rate of poorly differentiated ca, tumor weight | In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma. In the allograft model, HFD increased solid tumor growth and the expression of proteins related to proliferation/angiogenesis. |
| Xu [42] | 2015 | TRAMP | HFD (40%) vs. ND (16%) | Tumor formation rate, survival | The mortality of TRAMP mice from HFD group was significantly higher than that of normal diet group (23.81% and 7.14%, p = 0.035). The tumor incidence of HFD TRAMP mice at 20th week was significantly higher than normal diet group (78.57% and 35.71%, p = 0.022) | |
| Xu [43] | 2015 | TRAMP | HF (40%) vs. ND (16%) | Tumor incidence, survival | TRAMP mice in HFD group had significantly higher mortality rates than those in the normal diet group (p = 0.032). The HFD group had a significantly higher tumor formation rate at age 20 weeks than the normal diet group (p = 0.045). | |
| Lo [44] | 2016 | SCID | PDX kidney capsule xenograft | HF (43%) vs LF (6%) | Pathology and biomarker expression | Prostate cancer tumorigenicity is not accelerated in the setting of diet-induced obesity or in the presence of human PPAT. |
| Liang [45] | 2016 | Immunocompetent FVB mice | MycCap alloraft | High ω-6 vs. ω-3 diet | Tumor volume | Tumor volumes were significantly smaller in the ω-3 than in the ω-6 group (p = 0.048). |
| Huang [46] | 2016 | BALB/c-nu/nu | LNCap xenograft | HFD (59.9%) vs LF (9.5%) | Intratumoral AKT and Extracellular Signal-regulated Kinase (ERK) activation, AMPK inactivation | HFD resulted in AKT and ERK activation and AMPK inactivation. |
| Labbe [47] | 2016 | Prostate specific Pten and Ptpn1 deletion mouse | HFD vs. chow | Microinvasive rate | PCa in Pten-/-Ptpn1-/- mice was characterized by increased cell proliferation and Akt activation, interpreted to reflect a heightened sensitivity to IGF-1 stimulation upon HFD feeding | |
| Kwon [48] | 2016 | 14K-creER PTEN (K14-CreER;Ptenfl/fl;mTmG (K14-Pten-mTmG) triple transgenic mice | HFD vs. RD | PIN 3/4 rate | HFD increased the number of PIN. | |
| Zhang [49] | 2016 | C57BL6 | RM1 mouse prostate cancer alloglaft | HFD (58%) vs. chow | Tumor growth | CXCL1 chemokine gradient was required for the obesity-dependent tumor ASC recruitment, vascularization and tumor growth promotion |
| Chang [50] | 2017 | C57BL6 | HFD (45%) vs. chow | Cav-1 secretion from adipose tissue | Cav-1 secretion was evident in adipose tissues and were substantially promoted in HFD-fed mice. | |
| Kim [51] | 2017 | SCID | PC-3 xenograft | 10%, 45%, or 60% fat | Tumor size, tumor weight | The 45% and 60% fat diets significantly promoted the growth of xenografts comparison to the 10% fat diet |
| Nara [52] | 2017 | a) BALB/c-nu/nu | a) LNCap xenograft, b) PC-3 and DU145 cultured with mice serum | HFD (59.9%) vs. CD (9.5%) | a) Tumor volume, b) cell proliferation | The tumor growth of prostate cancer LNCaP xenograft was significantly higher in the HFD group than in the CD groups. Cells cultured with HFD mouse serum had higher proliferation. |
| Huang [53] | 2017 | BALB/c-nu/nu | Intraperitoneal injection PC-3M-luc-C6 | HFD (59.9%) vs. LF (9.5%) | Luciferase activity (IVIS), number of metastasis | HFD and PrSC increased luciferase activity and number of metastasis. |
| Hayashi [54] | 2018 | Prostate-specific Pten deletion mouse | HFD (62.2%) vs. CD (12.5%) | Tumor growth | HFD accelerated tumor growth alogn with the inflammatory response. | |
| Massillo [55] | 2018 | C57BL/6J | TRAMP C1 allograft | HFD (37%) vs. CD (5%) | Tumor volume | HFD significantly increased tumor growth and serum estradiol in mice. |
| Chen [56] | 2018 | Prostate specific Pten and Pml deletion mouse | HFD (60%) vs. chow (17%) | Rate of mice having metastases | A HFD-derived metastatic progression and increases lipid abundance in prostate tumors | |
| Hu [57] | 2018 | TRAMP | HFD (40%) vs. CD (16%) | Proportion of poor tumor differentiation and tumor metastasis | A trend toward poorer PCa differentiation was observed in HFD-fed mice, while no statistical significance was detected. |
Abbreviations: HFD: high-fat diet, LFD: low-fat diet, HC: high-calorie diet, LC: low-calorie diet, NKCD: high-fat/no-carbohydrate ketogenic diet, WD: Western-style diet, CR: calorie restriction, Ab: antibody, SD: standard diet, CD: control diet, PDX: patient-derived xenograft, NWD: new Western-style diet.