研究甘草查爾酮A抗肺癌細胞侵襲機制

壹. 中文摘要近二十年來肺癌成為全球發生率及死亡率最高之疾病，台灣國民健康局公告公布台灣地區肺癌是十大死因之首惡性腫瘤，平均約有百分之八十的癌症病人因癌細胞之轉移而致命，故若能有效抑制癌細胞的轉移及入侵，將可大幅減低癌症的死亡率。而傳統的抗癌化療藥物對於癌症患者產生了相當多的後遺症及不適感，因此發展天然藥物來當作癌症預防或是治療藥物是目前最重要的課題。甘草查爾酮A (Licochalcone A; LicA)是甘草成分中最具有活性的化合物，且本身也是estrogenic 且屬於黃酮類分子。目前甘草查爾酮A 被證實具有抗腫瘤、抗轉移、抗發炎、抗血管新生和誘導細胞自噬和凋亡等多重生物功用。但是，目前甘草查爾酮A對於人類肺細胞癌的作用機制，至今仍然未知。本研究以MTT方式證實甘草查爾酮A不會降低人類肺癌細胞株（A549）及正常人類肺細胞(WI38) 的細胞存活率。腫癌細胞的侵襲和轉移是惡性腫瘤的重要特徵之一，因此本研究以高度侵襲非小細胞肺癌（A549）證實甘草查爾酮A抑制A549細胞移動和侵襲的能力。利用西方墨點法方式證實甘草查爾酮A抑制A549細胞移動和侵襲是透過抑制 MMP1和MMP3路徑的表現；同時也證實甘草查爾酮A會抑制Akt的磷酸化表現。為了證實甘草查爾酮A是否透過Akt活化途徑來影響MMP-1和MMP-3表現，我們加入Akt抑制劑(LY294002)會加強甘草查爾酮A抑制MMP1和MMP3路徑的表現，同時也會加強抑制細胞移動和侵襲能力。此外，轉殖活化態Akt(CA-Akt)證實轉殖活化態Akt(CA-Akt)會減緩甘草查爾酮A抑制MMP1和MMP3路徑的表現，同時也會減緩抑制細胞移動和侵襲能力。綜合以上實驗結果說明甘草查爾酮A可能在作為抗肺癌侵襲藥物的發展上具有重要的潛在能力。

關鍵字

研究甘草查爾酮A

並列摘要

Lung cancer is the highest cause of mortality and incidence in the world. In Taiwan, Bureau of Health Promotion, Department of Health, R.O.C.(Taiwan) published that lung cancer is number one of our top 10 causes of death Lung cancer. The metastasis (invasion) of cancer cells leads 80% patients died, and inhibition of cancer cells metastasis will markly decrease the death rate. Therefore, development of novel nature drug or drug therapy was important topic. Licochalcone A is the main active compound of the licorice species Glycyrrhiza inflate, and is an estrogenic flavonoid with anti-tumor, anti-metastatic, anti-inflammatory, anti-angiogenic activities, and induces autophagy and apoptosis. However, The effect molecular mechanism of Licochalcone A in human lung cancer is presently unknown. The goal of this study is to understand how Licochalcone A affects lung cancer cell proliferation and invasion. Our studies found that Licochalcone A in lung cancer A549 cells and normal lung WI38 cells did not affect the cell growth by MTT assay. The crucial role played by ECM degradation in cellular invasion suggests that matrix-degrading proteinases are required to clarify whether or not MMPs family are involved in inhibition of migration and invasion by Licochalcone A. Our results showed Licochalcone A could inhibit the activation of Akt and was involved in the downregulation of the protein expressions and messenger RNA levels of matrix metalloproteinase-1 (MMP-1), and matrix metalloproteinase-3 (MMP-3). To understand whether the Licochalcone A affects the migration and invasion through the activation of Akt and MMP-1/3 pathways, a Akt specific inhibitor LY294002 was applied to the invasion /migration assays . The results showed that LY294002 cause reduced protein expression of MMP-1/3 and significantly reduced the migration and invasion in A549 cells . In addition, Licochalcone A significantly decreased the levels of MMP-1/3 in CA-Akt-transfected cells concomitantly with a marked reduction in cell migration and invasion. Therefore, Licochalcone A is a promising candidate for further development an anti-invasive agent against lung cancer progression.

並列關鍵字

Licochalcone A

參考文獻

[3] W. P. T. Hamilton, Round A, Sharp D., "What are the clinical features of lung cancer before the diagnosis is made? A population based case-control study. ," 2005.

[4] M. J. Thun, L. M. Hannan, L. L. Adams-Campbell, P. Boffetta, J. E. Buring, D. Feskanich, et al., "Lung cancer occurrence in never-smokers: an analysis of 13 cohorts and 22 cancer registry studies," PLoS Med, vol. 5, p. e185, Sep 30 2008.

[6] K. M. A. O'Reilly, Beckett WS, Sime PJ., " Asbestos-related lung disease," 2007.

[7] H. O. Al-Shamsi, A. Al Farsi, and P. M. Ellis, "Stage III Non-Small-Cell Lung Cancer: Establishing a Benchmark for the Proportion of Patients Suitable for Radical Treatment," Clin Lung Cancer, vol. 15, pp. 274-80, Jul 2014.

[8] K. Russell, B. Healy, J. Pantarotto, S. A. Laurie, R. MacRae, E. Sabri, et al., "Prognostic factors in the radical nonsurgical treatment of stage IIIB non-small-cell lung cancer," Clin Lung Cancer, vol. 15, pp. 237-43, May 2014.

國際替代計量

研究甘草查爾酮A抗肺癌細胞侵襲機制

全文下載

主題瀏覽