Over-consumption of
dietary fat has been suggested to promote the development and progression of
prostate cancer in men. The present study was conducted to answer the following questions: (a) Can
dietary fat reduction decrease
tumor growth rates of Los Angeles
prostate cancer (LAPC)-4 xenografts in severe combined immunodeficient (SCID) mice independent of total caloric intake? and (b) Is the
insulin-like growth factor (IGF) axis involved in the effects of
dietary fat on LAPC-4
tumor growth in SCID mice? Twenty-eight male CB17 beige SCID mice (8 weeks old) were individually caged, randomized, and fed an isocaloric high-fat (HF, 42% kcal) or low-fat (LF, 12% kcal) diet. Each mouse was s.c. injected with 1 x 10(5) LAPC-4 cells, and
tumor volumes were measured weekly. At week 16, all animals were sacrificed, and serum and
tumors were obtained for analysis. Although caloric intakes and mouse weights were equal between groups, the LF mice had significantly slower
tumor growth rates and lower serum
prostate-specific antigen levels compared with the HF mice. LF mice had significantly lower levels of serum
insulin,
tumor IGF-1 mRNA expression, and
tumor IGFBP-2 immunostaining and higher levels of serum
IGFBP-1 (by Western
ligand blot) relative to the HF mice. There were no differences in the serum levels of
IGFBP-3 and
IGFBP-4 between the groups. LAPC-4 cells cultured in vitro with media containing serum from LF mice demonstrated slower growth than LAPC-4 cells cultured in media containing HF mice serum. These results demonstrate that intake of an LF diet was associated with slower LAPC-4 prostate
tumor growth relative to mice fed an HF diet, independent of total caloric intake, and this effect may be mediated through modulation of the
insulin/IGF axis.