ω-3 PUFA通过抑制DPD和TS促进5-FU抗SW480移植瘤的作用  

ω-3 PUFA promoting the inhibitory effect of 5-FU on SW480 xenografts by inhibiting DPD and TS

作　　者：谭耀宗[1] 黄文革[2] 周静雅[1] 杨阳[1] 朱惠莲[1] 

机构地区：[1]中山大学公共卫生学院,广东广州510080 [2]中山大学实验动物中心

出　　处：《华南预防医学》2013年第3期12-16,共5页South China Journal of Preventive Medicine

摘　　要：目的研究ω-3多不饱和脂肪酸(ω-3 PUFA)联合5-氟尿嘧啶(5-FU)对SW480移植瘤的抑制作用以及对二氢嘧啶脱氢酶(DPD)、胸苷酸合成酶(TS)蛋白表达的影响。方法用BALB/C nu/nu裸小鼠建立SW480移植瘤模型,随机分成4个组(每组8只),并给予含有不同比例ω-3 PUFA的饲料:基础饲料组(总脂肪5%,含ω-3 PUFA 0.3%)、ω-3对照组(总脂肪20%,含ω-3PUFA 0.3%)、低ω-3组(总脂肪20%,含ω-3 PUFA 2.9%)和高ω-3组(总脂肪20%,含ω-3 PU-FA 4.8%),每3 d给予35 mg/kg的5-FU注射,饲养21 d,测定肿瘤重量,采用气相色谱法测定裸小鼠血清中ω-3 PUFA含量,并用蛋白印迹法(Western Blot)检测肝脏DPD、肿瘤TS蛋白表达量。结果移植肿瘤块后,32只裸小鼠一般情况良好且建模成功。ω-3对照组、低ω-3组和高ω-3组的肿瘤重量分别为(0.73±0.15)、(0.51±0.15)、(0.36±0.17)g,高ω-3组低于ω-3对照组(P<0.01);高ω-3和低ω-3组裸小鼠血清中的的ω-3 PUFA含量分别为17.13%、12.26%,均高于ω-3对照组(3.10%)(均P<0.01);高ω-3组、低ω-3组DPD相对表达量分别为0.19、0.61,均低于ω-3对照组(表达量为1)(P<0.05,P<0.01);随着饲料中ω-3 PUFA含量的增加,肿瘤重量下降(R2=0.53)、血清中ω-3 PUFA升高(R2=0.79)、肝脏中DPD的表达降低(R2=0.71)(均P<0.01)。高ω-3组和低ω-3组的游离型TS表达量分别为0.40、0.36,均比ω-3对照组(表达量为1)低,结合型TS表达量分别为0.42、0.25,亦低于ω-3对照组(均P<0.01)。结论ω-3 PUFA可能通过抑制肝细胞DPD和肿瘤细胞TS蛋白的表达来促进5-FU抗结直肠癌的作用。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 fi）r 21 days and injected with 5-Fu （35 mg/kg） every 3 days. The tumor weights were measured. The serumω-3 PUFA composition was determined by gas chromatograph. The liver DPD and tumor TS protein expres- sion 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 ser-um to-3 PUFA of nude mice in high ω-3 group and low ω-3 group were 17. 13 % and 12. 26 %, respec- tively, and both higher than that ofω-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 expression as 1 ） （P 〈0. 05 ,P 〈 0. 01 ）. As the dietaryω-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 gr

关 键 词：脂肪酸类 ω-3 氟尿嘧啶 结肠肿瘤 直肠肿瘤 胸苷酸合成酶 

分 类 号：R735.3[医药卫生—肿瘤]