Abstract:[Abstract] Objective: To investigate the effect of C5a on the proliferation and migration of non-small cell lung cancer (NSCLC) cells and its potential molecular mechanism. Methods: The C5a receptor (C5aR) expression in the human normal bronchial epithelial cell line BEAS-2B and three NSCLC cell lines (H1703, PC9, H1299) examined by RT-PCR and western blot (WB) analysis; PC9 cell were stimulated with various concentrations of C5a, and cell proliferation and migration by CCK-8 and scratch test; The PC9 cells were treated with C5a, and then the expression and phosphorylation of Akt1, ERK1/2 and PKC-α at different time points by WB; PC9 cells were respectively treated with Akt1 inhibitor (Perifosine) and ERK1/2 inhibitor (U0126) followed by C5a stimulation, WB was used to examine the expression and phosphorylation level of Akt1 and ERK1/2 and their upstream and downstream regulatory relationships. The effected of Perifosine and U0126 on PC9 cells proliferation and migration by CCK-8 and scratch test. Results: The expression level of C5aR in PC9 cells is significantly higher than that of other cells; C5a can significantly promote the proliferation and migration of PC9 cells; The phosphorylation levels of Akt1 and ERK1/2 were all markedly enhanced in the PC9 cells induced by C5a, but the total protein expression did not show significant change; Akt1 and ERK1/2 inhibitors can significantly down-regulate the proliferation and migration caused by C5a stimulation of PC9 cells, and Akt1 inhibitors can not only attenuate the phosphorylation of Akt1, but also attenuate the phosphorylation of ERK1/2, and ERK1/2 inhibits The agent can only attenuate its own phosphorylation. Conclusion:C5a induces the proliferation and migration of NSCLC cells through the activation of Akt1/ERK1/2.