Luo Weimin, Liu Yuefeng, Zhang Jun, Luo Xiangyu, Lin Chenyi, Guo Jialong
Department of Cardiothoracic Surgery, Taihe Hospital Affiliated to Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Exp Ther Med. 2013 Sep;6(3):743-746. doi: 10.3892/etm.2013.1196. Epub 2013 Jul 2.
This study aimed to determine the effect of andrographolide (AD) on the growth of H3255 lung cancer cells and its possible impact on the expression and activity of the matrix metalloproteinase (MMP)-9 protein. H3255 cells were cultured , and treated with AD (1, 5 or 10 μM) for 24, 48 or 72 h. Cell proliferation was detected using an MTT assay and the expression of MMP-9 mRNA was measured using a reverse transcription-polymerase chain reaction (RT-PCR). The activity of MMP-9 was assessed by gelatin zymography, while the nuclear translocation of the nuclear factor-κB (NF-κB) p65 subunit and the phosphorylation of IκB were determined by western blotting. AD inhibited the proliferation of the H3255 cells in a concentration- and time-dependent manner, in addition to downregulating the expression of MMP-9 mRNA and the activity of MMP-9. Moreover, AD significantly inhibited the nuclear translocation of the NF-κB p65 subunit and suppressed IκB phosphorylation. The significant inhibition of H3255 cell proliferation by AD may have been correlated with the reduction in MMP-9 expression and activity through the inhibition of the phosphorylation of IκB and the translocation of NF-κB. The results suggest that AD is a promising drug candidate for the treatment of the migration and invasion of malignant tumors.
本研究旨在确定穿心莲内酯（AD）对H3255肺癌细胞生长的影响及其对基质金属蛋白酶（MMP）-9蛋白表达和活性的可能影响。培养H3255细胞，并用AD（1、5或10μM）处理24、48或72小时。使用MTT法检测细胞增殖，使用逆转录-聚合酶链反应（RT-PCR）测量MMP-9 mRNA的表达。通过明胶酶谱法评估MMP-9的活性，同时通过蛋白质印迹法测定核因子-κB（NF-κB）p65亚基的核转位和IκB的磷酸化。AD以浓度和时间依赖性方式抑制H3255细胞的增殖，此外还下调MMP-9 mRNA的表达和MMP-9的活性。此外，AD显著抑制NF-κB p65亚基的核转位并抑制IκB磷酸化。AD对H3255细胞增殖的显著抑制可能与通过抑制IκB磷酸化和NF-κB转位而导致的MMP-9表达和活性降低有关。结果表明，AD是治疗恶性肿瘤迁移和侵袭的有前景的候选药物。
