Wang Zhitian, He Tianyu, Lv Wang, Hu Jian
Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Transl Cancer Res. 2023 Feb 28;12(2):236-246. doi: 10.21037/tcr-22-2200. Epub 2023 Feb 14.
Metabolic reprogramming and epithelial-mesenchymal transformation (EMT) play an important role in lung cancer. In recent studies, metabolic enzymes such as Fructose-1,6-bisphosphatase 1 (FBP1) have shown potential functions beyond regulating metabolism.
Western blot assay was performed to detect glycolysis-related and EMT-related protein expression levels. The glucose uptake kit and adenosine triphosphate (ATP) detection kit were used to detect glucose uptake rate and ATP content. Transwell assay was used to determine the invasiveness of lung adenocarcinoma cells. Wound healing assay was used to determine the metastatic ability of lung adenocarcinoma cells. Methyl thiazolyl tetrazolium (MTT) assay and EdU staining were performed to investigate the effect of FBP1 overexpression on lung adenocarcinoma proliferation.
Overexpression of FBP1 down-regulated glycolysis-related protein levels and inhibited glucose uptake and ATP production, while knockdown of FBP1 had the opposite effect. Overexpression of FBP1 reversed EMT and inhibited Slug expression. Meanwhile, overexpression of FBP1 impaired the invasion, metastasis and proliferation ability of lung adenocarcinoma cells. In contrast, FBP1 knockdown promoted the EMT process, up-regulated Slug expression and enhanced the invasion, metastasis and proliferation of lung adenocarcinoma cells.
Therefore, FBP1 can be used as one of the potential clinical targets through inhibiting glycolysis, cell invasion and proliferation by inhibiting Slug mediated EMT processes.
代谢重编程和上皮-间质转化（EMT）在肺癌中起重要作用。在最近的研究中，果糖-1,6-二磷酸酶1（FBP1）等代谢酶已显示出超出调节代谢的潜在功能。
进行蛋白质免疫印迹分析以检测糖酵解相关和EMT相关蛋白表达水平。使用葡萄糖摄取试剂盒和三磷酸腺苷（ATP）检测试剂盒检测葡萄糖摄取率和ATP含量。采用Transwell实验测定肺腺癌细胞的侵袭能力。采用伤口愈合实验测定肺腺癌细胞的转移能力。进行甲基噻唑基四氮唑（MTT）实验和EdU染色以研究FBP1过表达对肺腺癌增殖的影响。
FBP1过表达下调糖酵解相关蛋白水平，抑制葡萄糖摄取和ATP产生，而敲低FBP1则产生相反的效果。FBP1过表达逆转EMT并抑制Slug表达。同时，FBP1过表达损害肺腺癌细胞的侵袭、转移和增殖能力。相反，FBP1敲低促进EMT进程，上调Slug表达并增强肺腺癌细胞的侵袭、转移和增殖。
因此，FBP1可通过抑制Slug介导的EMT过程来抑制糖酵解、细胞侵袭和增殖，从而作为潜在的临床靶点之一。
