Nutritional Conditions for Cell Growth Affect Anticancer Drug Sensitivity

Objectives: The concentration of nutrient substrates such as glucose (GC) and glutamine (GT) in conventional cell culture media does not necessarily match the actual concentration in blood. However, cancer cellular metabolism and the effects of anticancer drugs have been often evaluated using conventionally cultured cells. Therefore, we investigated the effects of nutrient substrate concentration in the culture medium on the proliferation, glucose metabolism, and sensitivity to the anticancer drug, 2-deoxyglucose (2DG) of oral squamous cell carcinoma (OSCC) cells.
Methods: OSCC cell line (HSC-2) was grown in three types of D-MEM media with varying nutrient-substrate concentrations [medium A (standard medium concentration; 1000 mg/L GC, 4.0 mmol/L GT), medium B (referred to the serum concentration in healthy subjects; 1000 mg/L GC, 0.5 mmol/L GT), and medium C (referred to the serum concentration in diabetic patients; 4500 mg/L GC, 0.5 mmol/L GT)]. The effect of differences in nutrient condition on proliferative capacity and glucose metabolic activity was evaluated, and organic acids in glucose-derived metabolites were also analyzed by HPLC. Furthermore, we also evaluated how nutritional conditions affected on the effects of 2DG on the proliferation and metabolism.
Results: In medium C, cell proliferative capacity and glucose metabolic activity were 1.8±0.6 times (p=0.06) and 2.1±0.8 times (p<0.05) higher than in medium A, respectively. The ratio of lactate to total acid production tended to be lower in medium C (35.9±6.0%) than in medium A (51.3±20.0%) (p=0.19). The inhibition rate of proliferative capacity by 10 mM 2DG tended to be weaker in medium C (21.0±10.5%) than in medium A (36.9±17.2%) (p=0.054).
Conclusions: Cells grown under high GC conditions showed higher proliferative capacity and glucose metabolic ability, but lower sensitivity to 2DG. Their metabolic pathway was also changed a little. These results suggest the importance of nutrient-substrate concentration management in blood in clinical cancer treatment.