Abstract:Objective: To investigate the inhibitory effect of metformin (MET) on the proliferation of esophageal squamous cell carcinoma (ESCC) KYSE-180 cells based on the homeobox protein B7 (HOXB7)/β-Catenin pathway. Methods: Human ESCC cells KYSE-180 were used as the research object. KYSE-180 cells were assigned into control group, MET-L group (0.5μmol/L), MET-H group (2μmol/L), MET-H+pcDNA-NC group (transfected with pcDNA-NC+2μmol/L MET), and MET-H+pcDNA-HOXB7 group (transfected with pcDNA-HOXB7+2μmol/L MET). Methyl thiazolyl tetrazolium (MTT) was used to detect cell proliferation. Transwell experiment and scratch assay were used to detect cell migration and invasion. Flow cytometry was used to detect the apoptosis rate of cells. In addition, real-time quantitative fluorescent PCR (qRT-PCR) and Western blot was used to detect the expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)-9, HOXB7, and β-Catenin proteins in cells. A xenograft tumor mouse model was established to evaluate the anti-cancer effect of MET in vivo and its effect on HOXB7 and β-Catenin expression. Results: Compared with the control group, the MET-L group and MET-H group had lower HOXB7, β-Catenin mRNA expression, A490 value, cell migration number, scratch healing rate, cell invasion number, and PCNA, MMP-9, HOXB7, and β-Catenin protein expression (P<0.05), and higher apoptosis rate (P<0.05). Compared with the MET-H group and the MET-H+pcDNA-NC group, the MET-H+pcDNA-HOXB7 group had higher HOXB7, β-Catenin mRNA expression, A490 value, cell migration number, scratch healing rate, cell invasion number, and PCNA, MMP-9, HOXB7, and β-Catenin protein expression (P<0.05), and lower apoptosis rate (P<0.05). After MET treatment, tumor volume, tumor weight, HOXB7, β-Catenin protein expression decreased, TUNEL positive rate increased (P<0.05); overexpression of HOXB7 weakened the effect of MET on the above indexes (P<0.05). Conclusion: MET can inhibit the proliferation of ESCC KYSE-180 cells, and its mechanism may be achieved by inhibiting the HOXB7/β-Catenin pathway.
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