葡萄糖转运蛋白在丁酸钠诱导结肠癌细胞凋亡中的作用

Role of glucose transporters in apoptosis induced by sodium butyrate

目的观察丁酸钠对结肠肿瘤细胞HT-29葡萄糖转运蛋白(GLUT1～GLUT5)表达的影响以及丁酸钠和不同浓度葡萄糖对bax和bcl-x/l表达的影响,探讨丁酸钠诱导肿瘤细胞凋亡的可能机制。方法2005年4月至12月在武汉大学人民医院应用逆转录-聚合酶链反应(RT-PCR)检测GLUT1～GLUT5mRNA的表达情况。免疫细胞化学法检测bax和bcl-x/l的表达。原位切口末端标记法(Tunel)检测细胞凋亡。结果丁酸钠明显抑制GLUT1和bcl-x/l表达并诱导肿瘤细胞凋亡,但对GLUT2、GLUT3、GLUT5和bax表达影响不大,GLUT4则未被检测出。丁酸钠干预条件下,葡萄糖浓度增加可以明显增加bcl-x/l的表达并降低丁酸钠诱导的细胞凋亡。无丁酸钠干预条件下,葡萄糖浓度变化对细胞凋亡影响很小。结论在HT-29细胞中,丁酸钠能明显降低GLUT1的表达。降低GLUT1的表达与丁酸钠诱导细胞凋亡作用密切相关。

Objective The regulation on glucose transporters （ GLUT1 - GLUT5 ） by sodium butyrate was observed, and the regulation on bax and bcl-x/l by sodium butyrate and glucose was studied. This helped to learn about the possible mechanism of apoptosis of cancer ceils induced by sodium butyrate. Methods The expression of GLUT1 - GLUT5 mRNA was detected by RT-PCR. The expression of bax and bcl-x/l was detected by immuocytochemistry. Cell apoptosis was detected by TUNEL assay. Results In HT-29 cell line, sodium butyrate downregulated the expression of GLUT1 mRNA and the expression of bcl-x/l and induced cancer cell apoptosis, but did not regulate the expression of GLUT2, GLUT3 , GLUT5 and bax. GLUT4 was not detected in HT-29 cell line. And when treated with sodium butyrate, the increase of concentration of glucose could increase the expression of bcl-x/l and reduce the effect of apoptosis induced by sodium butyrate. Without treatment with sodium butyrate, the change of glucose concentration only had a feeble regulation on apoptosis. Conclusion Sodium butyrate can obviously downregulate the expression of GLUT1 and downregulation of the expression of GLUT1 is associated with the apoptosis induced by sodium butyrate in HT-29 cell line.