Metformin Influenced Glucose Metabolic Activity of Cancer Cells.

Objectives: Metformin is a first-line drug for the treatment of type 2 diabetes, but there is increasing evidence of its potential efficacy as an anticancer drug. Several studies have shown the direct inhibitory effect of metformin on cancer cell growth and its activating effect on AMP-activated protein kinase (AMPK), an energy sensor that regulates cell metabolism. These findings suggest that metformin might inhibit cellular metabolism; however, there is still no direct evidence for the inhibitory effect of metformin on cellular metabolism. Therefore, the present study aimed to clarify the effect of metformin on the glucose metabolic activity of cancer cells.
Methods: Human oral squamous cell carcinoma cells (HSC-2) and human cervical carcinoma cells (HeLa) were used. These cells were cultured, and collected at 80-90% confluency. The glucose-induced metabolic activity of each cell was monitored for 10 min at 37°C or 43°C by a real-time monitoring system using a pH-stat (Scientific Reports 2017; 7(1): 10092) in the presence of metformin.
Results: Metformin (10 mM) increased the glucose metabolic activity of HSC-2 and HeLa at 37°C by 34.3±12.3% (p = 0.029) and 36.4±29.8% (p = 0.078), respectively, while this reagent decreased the glucose metabolic activity at 43°C by 34.9±8.39% (p = 0.065) and 40.5±22.1% (p = 0.0268), respectively.
Conclusions: The present study showed that metformin directly influenced the glucose metabolic activity of cancer cells in the short term. This result suggests that metformin alters the glucose metabolism in cancer cells through enzymatic regulation, and consequently suppresses cancer cell growth. Supported by KAKENHI (Challenging Research (Exploratory) no. 18K19629 to NT).