内毒素诱导非小细胞肺癌细胞增殖及其机制

Effects of Endotoxin on Tumor Proliferation in the Non-Small Cell Lung Cancer and Underlying Mechanisms

目的:研究内毒素对体外培养非小细胞肺癌(NSCLC)细胞株A549细胞增殖的影响及其机制。方法:不同浓度脂多糖(LPS)进行8-48h干预,MTT及细胞计数法检测其对A549细胞增殖的影响;EGFR中和抗体或COX-2抑制剂与LPS联合干预,检测其对A549细胞增殖及PGE2的影响。结果:LPS可引发A549细胞MTT活性和细胞计数显著增加,且呈现时间和剂量依赖性。LPS还可诱发PGE2水平显著升高。药物干预结果显示,抑制COX-2或EGFR可明显逆转LPS所引发的细胞增殖和PGE2水平升高趋势。结论:LPS可能通过激活EGFR和COX-2信号途径,诱导体外培养的非小细胞肺癌细胞增殖分化。肺部感染可能会加速非小细胞肺癌进展,并可能造成不良预后。

Objective： To investigate the effect of endotoxin on tumor proliferation in the non-small cell lung cancer and the underlying mechanisms. Methods： Different concentrations ofLipopolysaccharide （LPS） were intervented from 8 to 48 h. The effection of LPS on the proliferation of A549 cells with MTT and cell counting were tested. The intervention effect of the combination of EGFR neutralizing antibody or COX-2 inhibitors with LPS on the proliferation of A549 cells and PGE2 were tested. Results： LPS induced a time- and dose-dependent increase in proliferation of A549 cells as quantified by MTS activity and cell counting. Large amounts of COX-2-derived prostaglandin （PG） E2 were secreted from LPS-stimulated A549 cells. Pharmacological interventions revealed that inhibition of COX-2 and EGFR activity in A549 cells severely attenuated both PGE2 release and proliferation in response to LPS. Conclusion： LPS induces proliferation of NSCLC cells in vitro inhuman NSCLC specimen via EGFR- or COX-2-signaling. Pulmonary infection may thus directly induce tumor progression in NSCLC.