High-fat diet‑induced adipokine and cytokine alterations promote the progression of prostate cancer in�vivo and in�vitro

Abstract

High-fat diet (HFD) -induced obesity is associated with more aggressive and lethal prostate cancer (PCa) in males, although the exact underlying mechanisms remain unclear. In the present study, transgenic adenocarcinoma of mouse prostate (TRAMP) models fed on an HFD (40% fat) or a control diet (CD; 16% fat) were generated, and cancer differentiation, local invasion and metastasis were compared at 20, 24 and 28 weeks. Mouse sera from each group were collected, and adipokines and cytokines were measured using multiplex immunoassays. HFD-sera and CD-sera were additionally processed into conditioned media (2.5% mixed sera), and in vitro studies were conducted to determine the proliferation, migration and invasion of cancer cells when conditioned media were used for culture. In TRAMP mice, HFD feeding increased body weight and adipose tissue deposition, and promoted the progression of PCa, specifically with regard to poorer differentiation, increased local invasion and metastasis rate. Sera from HFD-fed TRAMP mice contained increased levels of leptin, and a time-dependent increasing trend in the levels of CC chemokine ligand (CCL)3, CCL4, CCL5 and CXC chemokine ligand (CXCL)10 was observed. However, no alterations were detected in the levels of adiponectin, interleukin (IL)-4, IL-5, IL-6, IL-12p70, interferon-γ, tumor necrosis factor-α, CCL2, CCL7, CCL11, CXCL1 and CXCL2. In vitro studies determined that HFD-sera-conditioned medium promoted proliferation, migration and invasion of DU145 cells, as compared with CD-sera-conditioned medium and serum-free medium. In conclusion, the results of the present study suggested that the circulating adipokine and cytokine alterations in response to excess adipose tissue deposition induced by HFD feeding contributed to PCa progression.

Lipid accumulation facilitates mitotic slippage-induced adaptation to anti-mitotic drug treatment

“…Alternatively, pro-tumourigenic factors could be altered by FA levels and saturation. It has been shown that fatty acids induce the expression and secretion of inflammatory cytokines such as IL-6, IL-8 and IL-1β via activation of NF-κB pathway in normal and cancer cells 45 – 47 . Indeed, our data revealed that C75 treatment suppressed the activation of NF-κB in post-slippage cells which supports the notion that increased FASN promotes the induction of post-slippage secretory factors.…”

Decreased Efficacy of Doxorubicin Corresponds With Modifications in Lipid Metabolism Markers and Fatty Acid Profiles in Breast Tumors From Obese vs. Lean Mice

“…Sectioning, deparaffinization and rehydration of tumor tissue samples was performed as previously described (32). Tumor tissue samples were stained for histological changes using haemotoxylin and eosin (H&E) staining.…”

Combined maternal and post‐weaning high fat diet inhibits male offspring's prostate cancer tumorigenesis in transgenic adenocarcinoma of mouse prostate model

“…Heterozygous TRAMP female mice (purchased from Jackson Laboratory, Bar Harbor, ME) were bred to non‐transgenic C57BL/6 male mice (Jackson Laboratory). The second‐generation TRAMP female mice and non‐transgenic male mice were selected by genotyping as previously reported . After weaning (postnatal day 21, P21), TRAMP female mice were randomly categorized into two groups and fed either control diet (16% of calories from fat, SLAC Inc., http://www.slaccas.com; Shanghai, China) or HFD (40% of calories from fat, SLAC Inc.,) before mating, during pregnancy, and into lactation (Table ).…”