Topical Area: Diet and Cancer
Objectives : Aims of this study were to investigate the effect of HF on anchorage-independent tumor spheroid formation and its’ working mechanisms of lung malignant tumor cells.
Methods : Human NSCLC cells A549 were cultured in control (C) medium (2.2 μM folic acid) or HF medium (10, 30, 50 μM folic acid) for 4 days. Cells were harvested to explore the self-renewal capacity of cancer cells by observing the anchorage-independent tumor spheroid formation. Meanwhile, the L-lactate assay were conducted to evaluate the lactate-generating state and the cell protein extract for the western blotting analysis to realize expression of energy metabolism related proteins in cells.
Results : The results showed that numbers of tumor spheroids in HF group were significantly higher than the control group. Besides, compared to C group, HF50 group showed significantly reduced lactate release into medium with highly accumulation in cellular lactate levels. The glycolytic-related protein expression of hexokinase II (HKII), lactate dehydrogenase (LDH) were increased and glucose transporter 1 (GLUT1), pyruvate dehydrogenase (PDH) were decreased in HF group. The signaling-related protein expression of insulin receptor substract-1 (IRS-1), hypoxia-inducible factor-1 alpha (HIF-1𝛼) were increased and PI3 kinase (PI3K), AMP-activated protein kinase (AMPK) were decreased in HF group.
Conclusions : Collectively, HF supplementation may reprogram glycolytic metabolism and increase anchorage-independent tumor spheroids formation to mediate malignant progress of NSCLC.
Funding Sources : Ministry of Science and Technology, Taiwan, R.O.C.