Low density lipoprotein (LDL)-mediated suppression of Lewis lung carcinomain hypercholesterolemic LDL receptor-deficient mice

An inverse relationship has been reported between cancer risk and cholester ol level, prompting the hypothesis that hypercholesterolemia may be protect ive against cancer. We tested this hypothesis by evaluating the growth of L ewis lung carcinoma in three different murine models of hypercholesterolemi a: Pluronic treated mice, apolipoprotein E (ApoE) deficient mice, and low d ensity lipoprotein receptor (LDL-R) deficient mice. Only the accumulation o f LDL-cholesterol in LDL-R deficient mice suppressed tumor growth. Accumula tion of chylomicrons, very low density lipoproteins (VLDL), and cholesterol -enriched remnants in the Pluronic treated mice and ApoE deficient mice did not inhibit tumor growth, even though mice in all three models were equall y hypercholesterolemic, Taken together, the experimental evidence from our studies indicate that high plasma cholesterol in the form of LDL-cholestero l could have a beneficial effect against cancer in vivo, (C) 1999 Academic Press.