OBJECTIVETo study the effect of hyperlipidemia on the prognosis and therapeutic response for colorectal cancer and to explore the associated mechanism.

METHODSThe hyperlipidemic subcutaneous heterotopic colorectal cancer orthotopic transplant model of nude mice was established by feeding high fat diet and performing transplantation. Seventy mice were divided into 7 groups with 10 mice in each group. Two groups were used as pre-experiment. The remaining 5 groups included 4 high-fat groups (G1 to G4), and 1 normal-diet control group (G5). G1, G2, G3, G4, and G5 received normal saline, capecitabine, simvastatin, capecitabine plus simvastatin and capecitabine respectively for 3 weeks. Changes of tumor volume, tumor weight, tumor growth rate and blood lipid parameters (TC, TG, HDL, LDL, Lpa, apoA and apoB) were observed.

RESULTSIn G1 to G4, TC, HDL, apoA, TG, LDL, Lpa, apoB increased, but only TC, HDL, apoA were significantly different as compared with G5 (P=0.020, P=0.001, P=0.001, P=0.911, P=0.249, P=0.681, P=0.053). The tumor in G1 grew fastest, and its growth rate was significantly different as compared with G2, G4, G5 except G3 (P=0.001, P=0.806, P=0.001, P=0.010). The tumor growth rate of G3 was lower than group G1, but higher than G2, G4, G5 with significant difference (P=0.001, P=0.002, P=0.016). The tumor of G5 grew faster than G2 and G4, but without significant differences (P=0.051, P=0.070). The tumor of G4 grew slowest without significant difference as compared to G2 (P=0.438). Compared with pre-administration, at the third week, the TC of G1 was increased [(3.8±0.4) mmol/L], while the other 4 groups decreased [G2 (2.8±1.8) mmol/L, G3 (2.9±0.7) mmol/L, G4 (1.4±0.9) mmol/L, G5 (2.1±0.2) mmol/L]. G4 decreased significantly (P=0.004). At the fifth week, the TC of all the 5 groups decreased, while the lipids of G4 were higher as compared to those at the third week. The TG, Lpa, ApoA were significantly decreased at the third week (all P<0.05), while no significant differences were found in HDL and apoB.

CONCLUSIONSA hyperlipidemia colon tumor model involving subcutaneous colon translocation and orthotopic transplantation of nude mice is successfully established. This model is an ideal research model for hyperlipidemia and colorectal cancer. The effect of capecitabine on tumors in hyperlipidemia groups is better as compared to normal diet group. The proliferation of tumor cells can increase serum total serum cholesterol.