title: Decreased growth of established human prostate LNCaP tumors in nude mice fed a low-fat diet.
abstract: BACKGROUND
  Geographic variation in the incidence of clinically detected prostate cancer is considerable, with a 120-fold greater incidence in the United States than in China. The incidence of latent prostate cancer, however, shows little variation worldwide, with approximately 30% of men older than age 50 years having microfocal disease (determined by autopsy). Some epidemiologic studies have suggested that a high intake of dietary fat may constitute a risk factor for the development of advanced prostate cancer.
  
  
  OBJECTIVE
  We studied the influence of dietary fat content on the growth of tumors established in athymic nude mice with androgen-sensitive, human prostatic adenocarcinoma cells (LNCaP cells). We also investigated whether manipulation of dietary fat content altered prostate-specific antigen (PSA) production by these tumors.
  
  
  METHODS
  Tumors were induced in nude mice by subcutaneous injection of 10(6) LNCaP cells. Both the American Type Culture Collection (ATCC) LNCaP cell line and a more androgen-responsive subline derived from it (i.e., the Harris LNCaP cell line) were used. Mice were fed a 40.5-kcal% fat diet at the time of tumor cell injection. Three weeks later, after measurable tumors were formed, the animals were assigned to receive diets with one of the following fat contents: 40.5, 30.8, 21.2, 11.6, or 2.3 kcal% fat. Food intake, animal weights, and tumor volumes were recorded weekly; serum PSA and testosterone levels were measured at the termination of the study. Post hoc multiple comparisons were made using the Student-Newman-Keuls procedure. Two-sided tests of statistical significance were used to evaluate pairwise comparisons.
  
  
  RESULTS
  Tumor growth rates, final tumor weights, and ratios of final tumor weights to animal weights were substantially greater in groups that continued to receive a 40.5-kcal% fat diet than in groups whose diets were changed to 2.3 kcal%, 11.6 kcal%, or 21.2 kcal% fat (all P values < .04). Comparison of these parameters among the 2.3-kcal%, 11.6-kcal%, and 21.2-kcal% dietary fat groups did not reveal any statistically significant differences. No statistically significant differences were noted in total ingested calories, animal weight gain, serum testosterone levels, or histopathologic characteristics of the tumors among the tested dietary groups. Serum PSA levels were highest in the 40.5-kcal% fat group and lowest in the 2.3-kcal% fat group (evaluated only for ATCC LNCaP cells; P < .05).
  
  
  CONCLUSIONS
  Reduction of dietary fat substantially slows the growth of tumors established from human prostatic adenocarcinoma cells in a murine xenograft model. A positive association persists between tumor volumes and serum PSA levels even after extreme modification of dietary fat content.
authors.affiliation: Department of Surgery, Sloan-Kettering Institute for Cancer Research, New York, NY 10021, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: J G
authors.initials: JG
authors.lastname: Corr
authors.forename: H T
authors.initials: HT
authors.lastname: Thaler
authors.forename: Y
authors.initials: Y
authors.lastname: Tao
authors.forename: W R
authors.initials: WR
authors.lastname: Fair
authors.forename: W D
authors.initials: WD
authors.lastname: Heston
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000096:biosynthesis* / Q000097:blood; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D013739:Testosterone / Q000097:blood; D014407:Tumor Cells, Cultured
chemical_list: D004041:Dietary Fats; D013739:Testosterone; D017430:Prostate-Specific Antigen