瘦素对5-氟尿嘧啶损伤结肠癌细胞的影响  

Protective effect of leptin on human HT-29 cell injury induced by 5-fluorouracil

作　　者：王晓玲[1] 沈志祥[1] 沈磊[1] 于皆平[1] 罗和生[1] 滕小军[1] 郭洁[1] 

机构地区：[1]武汉大学人民医院消化内科,湖北武汉430060

出　　处：《中国药理学通报》2006年第4期492-496,共5页Chinese Pharmacological Bulletin

摘　　要：目的探讨不同浓度的瘦素对5-氟尿嘧啶(5-FU)损伤结肠癌细胞的影响。方法同时用5-FU及不同浓度的瘦素进行体外干预结肠癌HT-29细胞株。MTT法检测5-FU50%细胞生长抑制率(IC50)的变化。流式细胞仪、原位末端转移酶标记法(TUNEL)进行周期及凋亡分析。以RT-PCR方法检测caspase-9,caspase-3mRNA的表达。结果瘦素抑制5-FU对HT-29的杀伤作用。抑制5-FU诱导的细胞周期阻滞及细胞凋亡。RT-PCR表明加入瘦素后caspase-9,caspase-3mRNA的表达均下降,且呈剂量依赖性。结论瘦素通过下调caspase-9,caspase-3的表达促进结肠癌细胞产生凋亡抵抗,抑制5-FU的损伤作用。Aim To investigate whether leptin can affect the injury induced by 5-fluorouraeil （5-FU） on human colon cancer cell line HT-29 and examine the mechanisms involved. Methods HT-29 cells were cultured in vitro and 5-FU was given with or without different doses of leptin. The 50% cell inhibitory concentrations （IC50） after treatment with 5-Fu were determined by MTT assay. The cell cycle and apoptosis were analyzed using flow cytometry and TUNEL. caspase-9 and caspase-3 were evaluated by RT-PCR. Results Leptin enhanced HT-29 cell proliferation. In addition, leptin counteracted 5-FU-induced cell cycle arrest and apoptosis. RT-PCR analysis demonstrated that the expression levels of caspase-9 and caspase-3 were reduced dose-dependently after leptin exposure. Conclusions Leptin exerted antiapoptotic effects on HT-29 cells and protective effects aganist 5-FU via down-regulation of two key genes of the death cascade, caspase-9 and caspase-3.

关 键 词：结肠癌细胞 瘦素 5-氟尿嘧啶 凋亡 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R329.28[医药卫生—基础医学]