Effect and Mechanism of Metformin on Side Population Cells of Human Esophageal Squamous Cell Carcinoma

Objective To explore the effect and mechanism of metformin(Metf) on side population(SP) cells of human esophageal squamous cell carcinoma.

Methods We detected SP ratio of different esophageal squamous cell lines and sorted of SP cells by flow cytometry. The effects of metformin on the proliferation of SP cells in vitro were detected by CCK-8 method, plate cloning and sphere assay. The effect of Metf on the expression of SP cell-associated gene protein was detected by Western blot.

Results The SP ratio of the nine esophageal squamous carcinoma cell lines in this experiment was 0.2%-2%. Metf could reduce the SP ratio of KYSE 150, significantly inhibiting the cell proliferation, the number of clones and the number of spheres of SP cells. The degree of inhibition was positively correlated with Metf concentration and administration time. The difference is statistically significant (P < 0.01). In addition, Metf reduced the expression of the relevant stem genes SOX2 and OCT4 in SP cells to varying degrees.

Conclusion Metf could reduce the ratio of SP cells in esophageal squamous cell carcinoma, which may provide a new approach for the treatment and prevention of esophageal cancer.