Introduction

Inflammation could be associated with progression of prostate cancer. High fat diet (HFD) causes obesity and systemic inflammation, and might be associated with progression of prostate cancer. The aim of this study is to elucidate how HFD affects tumor progression and local immune cells using model mice for prostate cancer.

Methods

HFD or control diet (CD) had been administered to normal mice and model mice <Pb-Cre+;Ptenfl/fl)> until 22 weeks old. Tumor progression was evaluated by prostate weights, H&E staining, and Ki67 staining. The fractions of immune cells in the prostatic tissues were assessed by flow cytometry. We compared these factors of HFD-fed mice to CD-fed mice, and evaluated the changes of tumor progression and immune cells after administration of celecoxib (8mg/kg/day) to HFD-fed and CD-fed model mice.

Results

Prostate weights were significantly increased in HFD-fed model mice compared to CD-fed model mice (0.72 ± 0.57g vs 0.30 ± 0.14g, p =0.029), while there were no significant changes in between HFD-fed and CD-fed normal mice. Prostate cancer was pathologically more invasive, and the ratio of Ki67-positive cells to tumor cells of these areas was significantly increased in HFD-fed model mice compared to CD-fed model mice (30.0 ± 13.8% vs 7.8 ± 2.9%, p =0.002). The fraction of Myeloid-Derived Suppressor Cells (MDSCs) was significantly increased in HFD-fed model mice compared to CD-fed model mice (p =0.044). The M2/M1 macrophage ratio was significantly increased in HFD-fed compared to CD-fed model mice (p =0.011), while the ratio was significantly decreased in HFD-fed compared to CD-fed normal mice (p =0.037). Administration of celecoxib to HFD-fed model mice significantly decreased the prostate weights (0.28 ± 0.10g, p =0.040) and the ratio of Ki67-positive cells (8.3 ± 5.6%, p =0.005), and also decreased the fraction of MDSCs significantly (p =0.035) and the M2/M1 ratio (p =0.114). Administration of celecoxib to CD-fed model mice did not decrease the prostate weights.

Conclusions

HFD-induced pro-tumor changes of immune cells could accelerate tumor progression of prostate cancer, which was suppressed by celecoxib. Inflammation could be one of the key regulators for progression of prostate cancer.

Funding

none