关键词: 食管癌, 磷酸甘油变位酶1（PGAM1）, Warburg效应, 糖代谢, Akt／mTOR信号通路

Abstract: Objective  To investigate the effect of silencing phosphoglycerate mutase 1 （PGAM1） gene on the biological function of esophageal carcinoma cells and its possible mechanism. Methods  The expression of PGAM1 was detected by immunohistochemical SP method in 67 fresh esophageal cancer tissues and their adjacent normal tissues from July 2016 to June 2017. In order to analyze the effect of PGAM1 gene silencing on the apoptosis and proliferation of Eca-109 cells， PGAM1 shRNA （shPGM1 group） or shRNA-NC （NC group） was transfected into Eca-109 cells. QPCR and Western blotting were used to detect the effect of PGAM1 on the key molecules in Akt／mTOR signaling pathway. Results The high expression rate of PGAM1 in esophageal carcinoma was 58.2％ （39／67）， which was higher than that in adjacent tissues （31.3％）， and the difference was statistically significant （P＜0.05）. The expression of PGAM1 was correlated with clinical stage， differentiation degree and depth of invasion （P＜0.05）， but not with age， sex and lymph node metastasis （P＞0.05）. The expression of PGAM1 mRNA in shPGAM1 group and NC group were 0.48±0.10 and 1.01±0.14 respectively， and the difference was statistically significant （P＜0.05）. MTT assay showed that after 24， 48， 72 and 96 hours of culture， the proliferation rates Eca-109 cells in shPGAM1 group were （87.65±7.42）％， （79.34±9.11）％， （70.17± 6.84）％ and （60.36±7.95）％ respectively， which were significantly lower than those of NC group （P＜0.05）. The apoptosis rates of Eca-109 cells in shPGAM1 group and NC group were （45.36±5.38）％ and （24.81±4.67）％ respectively after 48 hours （P＜0.05）. The content of glucose in culture supernatant of Eca-109 cells in shPGAM1 group and NC group was （56.84±11.35）％ and （99.87±10.48）％， respectively. The content of lactic acid in culture supernatant of Eca-109 cells in shPGAM1 group and NC group was （48.02±10.18）％ and （99.00±12.35）％， respectively. The difference was statistically significant （P＜0.05）. The expression of PTEN in shPGAM1 group was higher than that in NC group （P＜0.05）， but the expression of p-Akt and p-mTOR was lower than that in NC group （P＜0.05）. Conclusion There are significant evidences that PGAM1 up-regulation would be related with esophageal cancer， which promote the proliferation of Eca-109 cells by activating the Akt／mTOR signaling pathway and Warburg effect.

Key words: Esophageal cancer, Phosphoglycerate mutase 1（PGAM1）, Warburg effect, Glucose metabolism, Akt／mTOR signaling pathway