丙酮酸脱氢酶激酶-1在人结肠癌中的表达及意义  

Expression of pyruvate dehydrogenase kinase-Ⅰ in human colon cancer and its significance

作　　者：童晶涛[1] 梁后杰[1] 陈建芳[1] 江恒[1] 谢赣丰[1] 刘平[1] 

机构地区：[1]第三军医大学西南医院肿瘤科,重庆400038

出　　处：《第三军医大学学报》2010年第3期257-260,共4页Journal of Third Military Medical University

摘　　要：目的检测丙酮酸脱氢酶激酶-I(pyruvate dehydrogenase kinase-I,PDK1)在人结肠癌组织和细胞中的表达。探讨抑制PDK1对结肠癌细胞活性的影响。方法应用RT-PCR、荧光定量PCR和免疫荧光法、Western blot检测结肠癌组织、癌旁组织以及4种人结肠癌细胞PDK1基因的表达情况。在PDK1抑制剂(dichloroacetate,DCA)的诱导下,通过MTT法观察结肠癌细胞活性。结果PDK1基因在结肠癌组织中表达较癌旁组织中高;在4种人结肠癌细胞中明显表达。抑制PDK1能抑制结肠癌细胞增殖活性,抑制效应随药物浓度而递增,其中90 mmol/L DCA的活性细胞率分别为(23.90±2.79)%、(5.90±1.31)%、(32.82±4.50)%和(29.72±3.03)%。结论PDK1基因在结肠癌组织和细胞中高表达,在癌旁组织中低表达,抑制PDK1明显抑制结肠癌细胞增殖活性,PDK1可望成为结肠癌有效治疗靶点。Objective To detect the expression of pyruvate dehydrogenase kinase-Ⅰ （ PDK1 ） in human colon cancer tissue and cells and to study the effect of PDK1 on colon cancer cell activity. Methods Expression of PDK1 in human colon cancer tissue and its adjacent tissue and 4 PDK1 genes in human colon cancer cells was detected by RT-PCR, fluorescence quantitative PCR, immunofluorescence and Western blotting, respectively. Colon cancer cell activity induced by dichloroacetate （DCA）, a PDK1 specific inhibitor, was measured by MTT. Results The expression level of PDK1 gene was higher in colon cancer tissue than in its adjacent tissue. The 4 PDK1 genes were significantly expressed in human colon cancer cells. DCA inhibited the proliferation activity of colon cancer cells by suppressing PDK1 in a concentration-dependent manner. The activity rate of 90 mmoL/L DCA for colon cancer cells was （23.90 ± 2.79 ）% , （5.90 ± 1.31 ）% , （32.82 ± 4. 50 ） % and （29.72 ±3.03 ） % , respectively. Conclusion The expression level of PDK1 gene is high in colon cancer tissue and cells, and low in its adjacent tissue. DCA can suppress the proliferation activity of colon cancer cells by inhibiting PDK1, thus PDKI may become an effective target in therapy for colon cancer.

关 键 词：结肠肿瘤 糖原酵解 丙酮酸脱氢酶激酶-1 

分 类 号：R735.3[医药卫生—肿瘤] R345.5[医药卫生—临床医学]