ω-3多不饱和脂肪酸对肿瘤细胞Rho GTP酶翻译后修饰的影响  

Effect of ω-3 Polyunsaturated Fatty acid on Posttranslational Modifications of Rho GTPase in Tumor Cells

作　　者：张乾勇[1] 易龙[1] 冉莉[1] 

机构地区：[1]第三军医大学营养与食品卫生学教研室,重庆400038

出　　处：《现代生物医学进展》2012年第1期9-11,共3页Progress in Modern Biomedicine

基　　金：国家自然科学基金资助项目(30471465)

摘　　要：目的:观察ω-3多不饱和脂肪酸(ω-3 Polyunsaturated fatty acid,ω-3 PUFA)对人前列腺癌PC-3细胞和乳腺癌MDA-MB-231细胞Rho蛋白翻译后修饰的影响。方法:60μmol/L的二十碳五烯酸(eicosapentaenoic acid,EPA)和二十二碳六烯酸(docosahex-aenoic acid,DHA)处理PC-3和MDA-MB-231细胞24h后,检测EPA和DHA对法尼基蛋白转移酶活性的影响,对Rho蛋白的法尼基化修饰的影响,对Rho蛋白与GTP结合能力的影响。结果:EPA及DHA均能显著下调PC-3和MDA-MB-231细胞法尼基蛋白转移酶活性(P<0.01),抑制Rho蛋白(RhoA、Rac1、Rac2和Cdc42)的法尼基化修饰(P<0.01),并降低PC-3细胞Rho蛋白(RhoA、Rac1和Cdc42)与GTP的结合能力(P<0.05)。结论:ω-3 PUFA可能通过抑制肿瘤细胞Rho蛋白翻译后修饰,而影响肿瘤细胞的生物学特性。Objective： To investigate the effects of ω-3 Polyunsaturated fatty acid on the posttranslational modifications of Rho GTPases in human prostate cancer cell line PC-3 and human breast cancer cell line MDA-MB-231.Methods： After a 24h pretreatment with 60 μmol/L DHA or EPA,farnesyl protein transferase activity was assayed as the ability of cytosolic protein extracts to catalyze the prenylation of Ras.The pretreatment cells were metabolically labeled with 1mCi/flask of farnesylpyrophosphate for 1h or with 2mCi/flask orthophosphoric acid for 4 h.Cell lysates were immunoprecipitated by incubating with RhoA,Rac1,Rac2 and Cdc42 an-tibody.Transfer of farnesylpyrophosphate onto Rho GTPases was quantitated by scintillation counting.GTP-and GDP-bound Rho GTPases were determined.Results： After treated with EPA or DHA of 60μmol/L,the farnesyl protein transferase activity in PC-3 and MDA-MB-231 cells was deseased（P 0.01）.The posttranslational processing of Rho GTPases was inhibited by EPA and DHA（P 0.01）.A significant reduction（P 0.05） was observed in the percentage of GTP bound RhoA,Rac1 and Cdc42 in EPA-and DHA-treated cells compared with untreated cells.Conclusion： These results suggest that ω-3 PUFA could inhibit the posttranslational modifications of Rho GTPases.

关 键 词：前列腺癌 乳腺癌 RHO蛋白 ω-3 PUFA 翻译后修饰 

分 类 号：R730.231[医药卫生—肿瘤]