Role of PI3K/Akt pathway in hypoxic-activated calcium sensing receptor mediated A549 cell metastasis / 中国药理学通报

ABSTRACT

Aim: To explore the role of PI3K/Akt signaling pathway in A549 and A549/DDP cells metastasis mediated by hypoxic-activated calcium sensing receptor (CaSR). Methods: The A549 and A549/DDP cells in the logarithmic growth stage were randomly divided into control, hypoxia, hypoxia + GdCl3 (CaSR agonist), hypoxia + NPS2143 (CaSR inhibitor) and hypoxia + LY294002 (PI3K inhibitor) + GdCl3 group. The protein levels of CaSR, MMP-2 and p-Akt were analyzed by Western blot in A549 and A549/DDP cells under different treatment conditions. The effects of different treatment factors on the ability of cell migration and invasion were measured by wound scratch assay and transwell migration assay. The effects of different treatment factors on the secretion of matrix metalloproteinase-2 (MMP-2) protein by A549 and A549/DDP cells was analyzed by ELISA. Results: Compared with control group, hypoxia increased the protein expression of CaSR, enhanced cell migration ability, increased MMP-2 protein expression in cells and culture medium, and promoted Akt protein phosphorylation in A549 and A549/DDP cells. NPS2143 reduced the effect of hypoxia, GdCl3 amplified the effect of hypoxia, and LY294002 inhibited effect of hypoxia and GdCl3. Conclusions: Hypoxic-activated CaSR promotes A549 cell metastasis, and its mechanism may involve PI3K/Akt pathway.