1,25(OH)2D3 inhibits Lewis lung cancer cell migration via NHE1‐sensitive metabolic reprograming

Abstract

AbstractHigh prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25‐dihydroxy vitamin D3 (1,25(OH)2D3) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2D3 could be associated with the expression and activity of Na+/H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.