二甲双胍对人食管鳞癌侧群细胞的作用及机制

邵凯迪; 王留兴; 陆士新

doi:10.3971/j.issn.1000-8578.2019.18.1200

二甲双胍对人食管鳞癌侧群细胞的作用及机制

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

摘要

摘要:
目的探讨二甲双胍（metformin, Metf）对人食管鳞癌侧群（side population, SP）细胞的作用及机制。
方法通过流式细胞仪检测食管鳞癌细胞系SP比例及分选SP细胞，CCK-8法、平板克隆及成球实验检测Metf对SP细胞体外增殖的影响，Western blot法检测Metf对SP细胞相关基因蛋白表达的影响。
结果本实验中的9种食管鳞癌细胞系的SP比例在0.2%~2%左右。Metf能够降低KYSE 150 SP比例、明显抑制SP细胞的细胞增殖、克隆形成数和成球生长数，其抑制程度与Metf浓度及给药时间呈显著正相关性，差异有统计学意义（P < 0.01）。此外，Metf能不同程度地降低SP细胞中相关“干性”基因SOX2与OCT4的表达。
结论 Metf能抑制食管癌细胞中SP细胞，可能为食管癌治疗与预防提供新的途径。

Abstract:
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.

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