The effect of cholesterol on cancer growth and metastasis: Experimental study with LDL receptor knockout mice.

Abstract

e22071 Background: Cholesterol is an essential component for normal cell growth. However, epidemiological studies show cholesterol levels may be associated with cancer incidence. The Multiple Risk Factor Intervention Trial reported a significant inverse relationship between cholesterol levels and lung cancer. The effects of cholesterol on cancer growth and metastasis have not been established. The aim of the present study was to determine if cholesterol alters cancer growth or metastasis. Methods: The study used 48 wild-type mice and 18 LDL receptor knockout mice (LDLR-/-). Mice were randomized into 3 groups: Group I (wild-type mice fed normal chow, n=23); Group II (wild-type mice fed high lipid chow, n=25); Group III (LDLR-/- mice fed high lipid chow, n=18). Human melanoma cells were injected subcutaneously for the assessment of growth and intravenously for metastasis. Mice were followed for 4 weeks. At the end of the study, mice were weighed and autopsy was performed. Melanoma weight, metastasis, and blood cholesterol levels were evaluated. Data was analyzed using One-way ANOVA and Chi-square. Results: LDL-cholesterol level was significantly higher in Group III than Group I (1103±472 vs.28±6; p<0.01). There was no significant difference in melanoma weight (2.74g ±1.77, 2.98g±1.98 vs. 2.18g±1.59, P=0.56) among the three subcutaneous injection groups. Lung metastasis was observed in all intravenous injection groups (11/11 vs. 10/10 vs. 8/8). There was no difference in melanoma weight or metastasis between male and female mice (P>0.05). There was no difference in net weight gain among the subcutaneous injection groups (4.12g±2.50 vs. 2.64g±2.79 vs. 3.66g±1.96, P=0.30). However, among the intravenous injection groups, weight gain was observed in Group II (2.78g±2.67) and Group III (2.36g±1.73) and weight loss in Group I (-0.32g±1.34, P<0.003). Conclusions: Cholesterol has no effect on melanoma growth or metastasis in mice. A high cholesterol diet may reduce weight loss in animals with metastatic melanoma. Further study is warranted to determine whether similar results exist in other types of cancers and to evaluate a possible beneficial effect of high lipid diets on patients with metastatic cancers.