二氢青蒿素抑制胰腺癌PANC-1细胞GLUT1表达的实验研究

Dihydroartemisinin suppresses expression of GLUT1 through PI3K/Akt signal pathway in pancreatic cancer PANC-1 cells

目的研究二氢青蒿素对胰腺癌PANC-1细胞的抑制作用和对GLUT1表达的调节作用及相关的信号通路。方法使用不同浓度的二氢青蒿素(0μM、10μM和60μM)对胰腺癌PANC-1细胞进行干预。在不同时间点(0h、24h和48h)使用MTT法对PANC-1细胞活性进行测定。在干预48h后,使用qPCR对二氢青蒿素干预的PANC-1细胞GLUT1mRNA的表达水平进行测定。使用western blot对二氢青蒿素干预的PANC-1细胞GLUT1蛋白表达水平以及PI3K和Akt磷酸化水平进行测定。结果使用不同浓度二氢青蒿素(0μM、10μM和60μM)对胰腺癌PANC-1细胞进行干预后,细胞活性呈时间依赖性和浓度依赖性下降,差异均有统计学意义(P均<0.05)。二氢青蒿素干预48h后,胰腺癌PANC-1细胞GLUT1mRNA和蛋白的表达水平以及PI3K和Akt磷酸化水平水平呈浓度依赖性的下降,差异均存在统计学意义(P均<0.05)。结论本基础研究提示二氢青蒿素可以通过调控PI3K/Akt信号通路的活化水平下调胰腺癌PANC-1细胞GLUT1mRNA和蛋白的表达,并对肿瘤细胞的增殖有显著抑制作用。该实验结果为进一步二氢青蒿素应用于胰腺癌等肿瘤的临床治疗奠定了一定的基础。

Objective To study the anti-tumor role of dihydroartemisinin （DHA） in pancreatic cancer PANC-1 cells and its involving signal pathway. Methods Three different concentrations （0μM, 10μM and 60μM） of DHA were obtained in our study. At different time points （0h, 24h and 48h）, MTT assay was performed to analyze the cell viabili- ties of PANC-1 cells. QPCR was used to detect the mRNA expression of GLUT1. The protein expression of GLUT1 and activation （phosphorylation） of PI3K and Akt were explored by western blot. Results The cell viabilities of pancreatic cancer PANC-1 cells were concentration-dependently and time-dependently suppressed by DHA. Then, after 48 hours of interventions, we found that the mRNA and protein expression of GLUT1 and the phosphorylation of PI3K and Akt were all concentration-dependently attenuated by DHA in pancreatic cancer PANC-1 cells. Conclusion Dihydroartemisinin （DHA） could inhibit the tumor proliferation and reduce the expression of GLUT1 possibly by inactivation of PI3K/Akt signal pathway in pancreatic cancer PANC-1 cells.