L-Arginine Inhibites Proliferation of Human Lung Adenocarcinoma A549 Cells and Expression of PI3K/Akt Signaling Pathway

Objective To observe the effect of L-Arginine(L-Arg) on the proliferation and apoptosis of human lung adenocarcinoma A549 cells and related mechanism.

Methods MTT assay was used to detect the A549 cells viability treated with different concentrations of L-Arg(0, 16, 32, 64, 96, 128 mmol/L) for 24, 36, 48h. The morphology changes of cells were observed by microscope. Flow cytometry was used to detect the apoptosis rate and cell cycle distribution. Western blot was used to detect the activation status of phosphatidylinositol-3-kinases/Akt (PI3K/Akt) signal pathway.

Results (1) As the dose and time increased, L-Arg could significantly inhibit A549 cells proliferation (P < 0.05); (2) Compared with control group, L-arginine could significantly reduce the number of cells and change the morphology as the concentration increased; (3) The ratios of apoptosis and G₀/G₁ cell cycle distribution were significantly increased by high dose of L-Arg, especially at 48h(P < 0.05); (4) As the concentration increased, L-Arg significantly decreased the phosphorylation of p-Akt S473 and up-regulated the expression of pro-apoptotic protein Cleaved Caspase-3 and Bad(P < 0.05).

Conclusion L-Arg could inhibit A549 cells proliferation and induce apoptosis. The mechanism may be connected with the restraining of PI3K/Akt signal pathway inactivation and the up-regulated expression of Bad protein and Cleaved Caspase-3.