楊順發Shun-Fa Yang楊士樑Shih-Liang Yang醫學研究所2026-10-299999-12-312018https://handle.ncl.edu.tw/11296/973h26https://scholars.csmu.edu.tw/handle/123456789/36382多形性神經膠質母細胞瘤 (glioblastoma multiforme, GBM) 由於治療其轉移能力相對困難，因此被認為是較致命的腫瘤。穿心蓮內酯(Andrographolide)是穿心蓮提煉萃取出的成分，穿心蓮內酯已知具有抗發炎活性、抑制各種癌症的生長的能力；然而，其對 GBM 的影響仍不清楚。本篇研究中，我們使用了穿心蓮內酯來觀察其在人類 GBM 細胞中的抗轉移能力是否有影響。我們的結果發現，穿心蓮內酯可有效抑制GBM8401 和 U-251 細胞的遷移和侵襲能力。此外，穿心蓮內酯也可明顯抑制基質金屬蛋白酶(matrix metalloproteinase, MMP)-2的活性和表現。即時定量聚合酶連鎖反應 (Real-time PCR)和啟動子活性檢測的結果也顯示穿心蓮內酯可在轉錄階段抑制 MMP-2 的表現；我們發現其抑制作用與抑制轉錄因子 CREB 和 DNA 結合的活性以及 CREB 表現有關。另外我們也發現穿心蓮內酯會藉由 ERK 1/2 訊息傳遞途徑抑制GBM8401 細胞的遷移能力；而使用抑制劑阻斷 ERK 1/2 訊息傳遞途徑可使穿心蓮內酯抑制之MMP-2及細胞遷移能力有意義回復。綜上所述，CREB 是穿心蓮內酯抑制 GBM 細胞中 MMP-2 所調控之細胞轉移的重要因子。因此，穿心蓮內酯和 ERK 調制劑的合併應用與治療可能是預防 GBM 細胞轉移一個很好的方向。Glioblastoma multiforme (GBM) can be a fatal tumor because of difficulties in treating the related metastasis. Andrographolide is the bioactive component of the Andrographis paniculata. Andrographolide possesses the anti-inflammatory activity and inhibits the growth of various cancers; however, its effect on GBM cancer motility remains largely unknown. In this study, we examined the antimetastatic properties of andrographolide in human GBM cells. Our results revealed that andrographolide inhibited the migration and invasion abilities of GBM8401 and U-251 cells. Furthermore, andrographolide inhibited matrix metalloproteinase (MMP)-2 activity and expression. Real-time PCR and promoter activity assays indicated that andrographolide inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of CREB DNA-binding activity and CREB expression. Mechanistically, andrographolide inhibited the cell motility of GBM8401 cells through activatily extracellular-regulated kinase (ERK) 1/2 pathway, and blocking of the ERK 1/2 pathway could reverse MMP-2-mediated cell motility. In conclusion, CREB is a crucial target of andrographolide for suppressing MMP-2-mediated cell motility in GBM cells. Therefore, a combination of andrographolide and an ERK modulator might be a good strategy for preventing GBM metastasis.轉移基質金屬蛋白酶神經膠質母細胞瘤穿心蓮內酯MMPmetastasisGlioblastomaAndrographolidethesis