Retarding Novikoff tumor growth by altering host rat cholesterol metabolism

Tumor cells, in vitro, must derive the majority of their required cholesterol from their host milieu. To determine if limiting tumor-available cholesterol results in limited tumor growth in vivo, Holtzman rats were given 10 X 10(6) Novikoff ascites tumor cells subcutaneously. Prior to inoculation, animals received either distal small bowel exclusion or sham operation plus either standard chow or estrone-containing chow (0.0025% or 0.01%) diets. In three separate experiments it was shown that (1) tumor weight was positively correlated with whole plasma cholesterol levels (r = 0.495; P less than 0.05); (2) the lowest tumor weights were correlated with the lowest plasma cholesterol; (3) low density and very low density lipoprotein cholesterol levels were both individually and in combination positively correlated with tumor weight (R2 = 0.828; P less than 0.01); and (4) survival of subcutaneous tumor inoculated animals was significantly greater in those animals shown to have the lowest plasma cholesterol, 27 +/- 1 days versus 29 +/- 1 days; (P less than 0.05). These data support the concept that limiting tumor-available cholesterol by altering host cholesterol metabolism will limit tumor growth.