摘要
目的体外研究雷帕霉素靶蛋白复合物1(mTORC1)抑制剂对人胰腺神经内分泌肿瘤(pNET)细胞株BON增殖的影响,探讨谷氨酰胺(Gln)代谢在mTORC1抑制剂影响BON细胞增殖中的作用。方法体外培养人胰腺神经内分泌肿瘤细胞BON,分别用1、5、10、25、50、100nM的雷帕霉素处理后,应用CCK-8检测BON的生长抑制率。用100nM雷帕霉素处理BON细胞12h后,检测其对Gln的吸收水平。在无葡萄糖(Glc)和(或)无谷氨酰胺(Gln)的情况下,应用CCK-8检测BON的增殖情况以及流式细胞术检测细胞周期情况。结果雷帕霉素可明显抑制BON细胞的增殖,抑制率呈时间-浓度依赖性(P<0.05)。同时雷帕霉素影响BON对Gln的吸收,而BON明显依赖于Gln生长,Glc-/Gln+组、Glc-/Gln-组、Glc+/Gln-组生长速率较Glc+/Gln+组差异有统计学意义(P<0.05)。结论 mTORC1抑制剂可能通过影响Gln代谢抑制BON细胞的增殖。
Objective To evaluatethe effect of mTORC1 inhibitor on the proliferation in human pancreatic neuroendocrine tumors（pNET）cell line BON,to explore the function of glutamine metabolism in it.Methods In vitro cultured human pancreatic neuroendocrine tumors（pNET）cell line BON,BON cells were treated with different concentrations of rapamycin（1,5,10,25,50,100nM）for 12,24 h.Then CCK-8assay are used to calculate the growth inhibitory rate.Rapamycin treated with BON 12 h,test the glutamine uptake level compared with control.Then deprive of glucose and/or glutamine,CCK-8assay were used in observation of cell proliferation,cell cycle distribution was analyzed by flow cytomety.Results Rapamycin significantly inhibited the growth of BON cells in a time-and dose-dependent manner（P〈0.05）.Meanwhile,rapamycin can reduce the glutamine uptake level compared with control.BON obviously depends on glutamine for growth,without glucose and glutamine group have obvious difference in growth rate（P〈0.05）.Conclusion mTORC1 inhibitor can inhibit BON cells proliferation and influence the glutamine uptake level.suggesting that mTORC1 inhibitor might inhibit BON cells proliferation by influenced the glutamine metabolic pathway.
出处
《重庆医学》
CAS
北大核心
2015年第6期738-740,共3页
Chongqing medicine
基金
中国临床肿瘤学科学基金(Y-N2013-006)
