Huang Hung-Che, Tsai Lo-Lin, Tsai Jen-Pi, Hsieh Shu-Ching, Yang Shun-Fa, Hsueh Jung-Tsung, Hsieh Yi-Hsien
Visiting staff, Division of General thoracic Surgery, Department of surgery, Changhua Christian Hospital, Changhua, Taiwan.
Tumour Biol. 2014 Dec;35(12):12139-49. doi: 10.1007/s13277-014-2519-3. Epub 2014 Aug 23.
Licochalcone A (LicA), a major phenolic constituent of Glycyrrhiza inflata, has been reported to exhibit anti-tumor, anti-inflammatory, and anti-metastatic properties in various cancer cells and animal models. The aim of this study was to determine the anti-tumor effects of LicA on lung cancer cells. The results indicated that LicA exhibited effective inhibition of cell migration and invasion of A549 and H460 cells under non-cytotoxic concentrations. Furthermore, LicA was also found to significantly inhibit the proteins and messenger RNA (mRNA) expression of MMP-1 and MMP-3 in A549 cells. Moreover, treatment of A549 cells with LicA-inhibited activation of the phosphorylation of Akt and inhibition of Akt by LY294002 (PI3K inhibitor) or transfection with the constitutive active-Akt (CA-Akt) expression vector significantly abolished the LicA-inhibited migration and invasion through activation of the Akt pathway. Further mechanistic studies revealed that LicA inhibits Akt signaling pathways and downstream transcription factors Sp1 expression. These findings imply a critical role for Akt inhibition in the LicA-inhibited migration and invasion of lung cancer cells. Thus, LicA might be used as an anti-invasive agent in the treatment of lung cancer.
光甘草定（LicA）是胀果甘草的主要酚类成分，据报道，它在各种癌细胞和动物模型中具有抗肿瘤、抗炎和抗转移特性。本研究的目的是确定LicA对肺癌细胞的抗肿瘤作用。结果表明，在无细胞毒性浓度下，LicA对A549和H460细胞的迁移和侵袭具有有效抑制作用。此外，还发现LicA能显著抑制A549细胞中基质金属蛋白酶-1（MMP-1）和基质金属蛋白酶-3（MMP-3）的蛋白质和信使核糖核酸（mRNA）表达。此外，用LicA处理A549细胞可抑制Akt磷酸化的激活，而用LY294002（PI3K抑制剂）抑制Akt或用组成型活性Akt（CA-Akt）表达载体转染可通过激活Akt途径显著消除LicA抑制的迁移和侵袭。进一步的机制研究表明，LicA抑制Akt信号通路和下游转录因子Sp1的表达。这些发现表明Akt抑制在LicA抑制肺癌细胞迁移和侵袭中起关键作用。因此，LicA可能用作治疗肺癌的抗侵袭剂。
