Abstract: Objective To investigate whether pemetrexed can regulate the proliferation of lung adenocarcinoma cells. Methods Human lung adenocarcinoma cell line A549 was selected for cell resuscitation, culture and passage, and was divided into control group, low-dose and high-dose pemetrexed intervention group. CCK-8 assay was used to detect proliferation inhibition rate of A549 cells. Flow cytometry was used to detect cell cycle and apoptosis; Western blot was used to detect the difference between proteins related to apoptosis and to PI3K/AKT signal pathway function. Results With the increase of drug dose and treatment time, both inhibition rate to A549 cells proliferation and apoptosis were significantly increased.The expression of cleaved caspase-3 and Bad protein was also significantly increased while the expression of Bcl-2 protein was significantly decreased (P＜0.05 or P＜0.01). At 48 h of culture, with the increase of pemetrexed concentration, the proportion of G₀/G₁ phase of A549 cells increased significantly, while the proportion of S phase and G₂/M phase decreased significantly (P＜0.05 or P＜0.01);The expression of PI3K, AKT and p-AKT wassignificantly decreased (P＜0.05 or P＜0.01). Conclusions Pemetrexed can inhibit the proliferation and promote apoptosis of lung adenocarcinoma cell line A549, potentially through a mechanism of inhibiting PI3K/AKT signaling pathway.

Key words: pemetrexed, PI3K/AKT signal pathway, lung adenocarcinoma, cell proliferation