内毒素诱导非小细胞肺癌细胞增殖及其机制 李

摘要目的：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。

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

ABSTRACT Objective:To investigate the effect of endotoxin on tumor proliferation in the non-small cell lung cancer and the underlying mechanisms. Methods:Different concentrations of Lipopolysaccharide (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 inhuman NSCLC specimen via EGFR- or COX-2-signaling. Pulmonary infection may thus directly induce tumor progression in NSCLC.