Effect of GLUT1 Inhibition and Autophagy Modulation on the Growth and Migration of Laryngeal Carcinoma Stem Cells Under Hypoxic and Low-Glucose Conditions

GLUT1抑制及自噬调控对缺氧低糖条件下喉癌干细胞生长和迁移的影响

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作者:Xiao-Hong Chen, Jia Liu, Jiang-Tao Zhong, Shui-Hong Zhou, Jun Fan

Background

Enhanced glucose uptake and autophagy are means by which cells adapt to stressful microenvironments. In this study, we investigated the roles of glucose transporter-1 (GLUT-1) and autophagy in laryngeal carcinoma stem cells under hypoxic and low-glucose conditions. Materials and

Conclusion

Enhanced glucose uptake and autophagy maintain the tumor behaviors of CD133-positive laryngeal carcinoma stem cells under hypoxic and low-glucose conditions.

Methods

CD133-positive Tu212 laryngeal carcinoma stem cells were purified by magnetic-activated cell sorting and subjected to hypoxic and/or low-glucose conditions. Proliferation was evaluated using a cell-counting kit and a clone-formation assay, and migration capability was measured through a Transwell assay. Autophagy was assessed using transmission electron microscopy. Gene silencing was monitored using shRNA technology and autophagy regulation was manipulated using rapamycin, 3-MA, or chloroquine. Gene expression levels were evaluated by quantitative reverse transcription-polymerase chain reaction and protein levels were assessed via Western blotting.

Results

Compared to CD133-negative cells, CD133-positive cells showed increased proliferation and migration capabilities, and reduced apoptosis, under hypoxic or low-glucose conditions. CD133-positive cells also showed increased expression of GLUT-1 and autophagy activity. Finally, GLUT-1 knockdown or autophagy inhibition reduced the proliferation and migration of CD133-positive laryngeal carcinoma stem cells.

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