[Role of Notch 1 signaling and glycolysis in the pathogenic mechanism of adenomyosis]

OBJECTIVE: To investigate the expressions of glycolysis-related factors and changes in Notch1 signaling in endometrial tissues of adenomyosis (AM) and Ishikawa cells to explore the pathogenesis of AM. METHODS: Eutopic endometrial tissues were collected from 8 patients with AM and 8 patients with uterine fibroids matched for clinical characteristics (control group). The expressions of Notch1 signaling proteins and glycolysis-related factors in the collected tissues were detected using qRT-PCR and Western blotting, and the levels of glucose and lactic acid were determined. An Ishikawa cell model with lentivirus-mediated stable Notch1 overexpression was established for assessing cell survival rate with CCK-8 assay, cell migration and invasion abilities with Transwell migration and invasion assays, and glycolytic capacity by determining the extracellular acidification rate. RESULTS: Compared with those in the control group, the endometrial tissues in AM group showed significantly increased expression level of carbohydrate antigen 125 (CA125), increased mRNA expression levels of Notch1, HK2 and PDHA and protein expressions of Notch1, GLUT1, HK2, PKM and PDHA, lowered glucose level and increased lactate level. The Ishikawa cell models with stable Notch1 overexpression exhibited significantly increased cell survival rate with attenuated cell migration and invasion abilities and decreased glycolysis capacity and reserve. CONCLUSION: The Notch1 signaling pathway participates in the pathogenesis of AM possibly by regulating the proliferation, migration, invasion and glycolysis of endometrial cells.