青蒿琥酯对肺癌A549细胞侵袭能力及ICAM-1、MMP-9表达的影响

Effects of Artesunate on the Invasion of Lung Adenocarcinoma A549 Cells and Expression of ICAM-1 and MMP-9

背景与目的近年来研究发现抗疟药青蒿琥酯对肺癌细胞具有抑制效应,但其作用机制尚未完全阐明。本研究旨在探讨青蒿琥酯对肺癌A549细胞侵袭能力的影响。方法 MTT实验观察青蒿琥酯对体外培养的A549细胞增殖抑制作用;Transwell小室侵袭实验检测青蒿琥酯对体外A549细胞侵袭转移能力影响;构建A549细胞裸鼠皮下移植瘤模型,观察青蒿琥酯对A549细胞移植瘤的抑制作用,并采用Western blot检测A549细胞移植瘤ICAM-1和MMP-9蛋白表达的变化。结果 MTT实验表明1.25μg/L-5μg/L的低浓度青蒿琥酯对A549细胞增殖无明显抑制作用。Transwell小室体外侵袭实验表明,与对照组(96.33±6.41)比较,1.25μg/L青蒿琥酯即可抑制A549细胞侵袭转移(75.43±4.37,P<0.05)。移植瘤实验表明10 mg/kg青蒿琥酯不能抑制裸鼠A549细胞移植瘤的生长(P>0.05),但是可降低ICAM-1和MMP-9蛋白表达量(P<0.05)。结论青蒿琥酯可抑制A549细胞侵袭潜能,其机制可能与降低ICAM-1和MMP-9表达有关。

Background and objective Artesunate, an anti-malarial drug, elicits an inhibitory effect on pulmonary carcinoma. However, the mechanisms of artesunate activity on pulmonary carcinoma have not been completely elucidated. hTe aim of this study is to investigate the effect of artesunate on the invasion of human lung adenocarcinoma A549 cells. Methods hTe inhibitory effect of artesunate on the proliferation and invasion of A549 cells was determined in vitro by MTT assay and transwell chamber invasion assay, respectively. A nude mouse model of human lung A549 cell xenogratf tumor was established. hTe inhibitory effect of artesunate on the tumor of the mouse model as well as ICAM-1 and MMP-9 protein expressions were determined by Western blot. Results A low dose of artesunate ranging between 1.25μg/L and 5μg/L did not signiifcantly inhibit the proliferation of A549 cells in vitro. By contrast, 1.25μg/L artesunate inhibited the invasion of A549 cells in vitro as determined by transwell chamber invasion assay （96.33±6.41 vs 75.43±4.37, P〈0.05）. Although 10 mg/kg artesunate did not signiifcantly inhibit A549 xenogratf tumor proliferation （P〉0.05）, artesunate decreased the ICAM-1 and MMP-9 protein levels in the mouse model （P〈0.05）. Conclusion Artesunate could inhibit the invasion of human lung adenocarcinoma A549 cells by possibly downregulating ICAM-1 and MMP-9 expressions.