Abstract:

Objective To investigate the synergistic inhibitory effect of ω-3 polyunsaturated fatty acids(ω-3 PUFA) and 5-fluorouracil (5-FU) on colorectal cancer (CRC) and the protein expression of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS). Methods BALB/C nu/nu nude mice were used to establish SW480 human CRC xenografts model. Nude mice were randomized into 4 groups (8 for each) and fed with diets containing different levels of ω-3 PUFA: basic group (total fat 5%,ω-3 PUFA 0.3%),ω-3 control group (total fat 20%,ω-3 PUFA 0.3%), low ω-3 group(total fat 20%,ω-3 PUFA 2.9%) and high ω-3 group (total fat 20%,ω-3 PUFA 4.8%). Nude mice were fed for 21 days and injected with 5-Fu (35 mg/kg) every 3 days.The tumor weights were measured. The serum ω-3 PUFA composition was determined by gaschromatograph. The liver DPD and tumor TS protein expression were determined by Western Blot. Results All nude mice were in good condition and the xenograft model was successfully established after transplantation. The tumor weights of ω-3 control, low ω-3, and high ω-3 group were (0.73±0.15) g, (0.51±0.15) g, and (0.36±0.17) g respectively, and the tumor weight of high ω-3 group was significantly lower than that of ω-3 control group (P<0.01). The serum ω-3 PUFA of nude mice in high ω-3 group and low ω-3 group were 17.13% and 12.26%, respectively, and both higher than that of ω-3 control group (3.10%) (both P<0.01). The DPD expressions of high ω-3 group and low ω-3 group were 0.19 and 0.61 and both lower than that of ω-3 control group (the expressionas 1) (P<0.05, P<0.01). As the dietary ω-3 PUFA increased, the tumor weight was decreased(R2=0.53), the serum ω-3 PUFA was increased (R2=0.79) and the expression of liver DPD was decreased (R2=0.71) (all P<0.01). The tumor free TS expressions of high ω-3 and low ω-3 groups were 0.40 and 0.36 and both lower than that of ω-3 control group (the expressionas 1), and the tumor combined TS expressions of high ω-3 and low ω-3 groups were 0.42 and 0.25 and lower than that of ω-3 control group (all P<0.01). Conclusion ω-3 PUFA can promote the inhibitory effect of 5-FU on CRC probably by inhibiting liver DPD and tumor TS expression.