本研究是經由探討細胞增生、細胞週期、細胞壞死或細胞凋亡等 機轉,以評估大黃酚對於人類肝癌細胞Hep3B 及肺癌細胞 A549 的生 長抑制作用與其可能作用機轉。實驗發現大黃酚經由活化 p21、p27 及 p53 使細胞停滯在 S 期(圖 7-1),同時對 Hep3B 與 A549 細胞的 增生有抑制作用;且ROS 上升伴隨著細胞質鈣離子濃度上升,粒線 體膜電位下降,ATP 濃度下降,造成染色體 DNA 裂解,最後使細胞 走向壞死;大黃酚同時也能干擾Hep3B 與 A549 細胞 PI3K 及 ERK 的 活性,導致NF-κB 及 COX-2 的生合成降低,進而降低 MMPs 的表現 量,使的細胞的轉移能力受抑制。
綜合上面的論述,大黃酚的抗癌活性除了可以抑制人類肝癌細胞 Hep3B 及肺癌細胞 A549 轉移外,對於抑制人類肝癌細胞 Hep3B 及肺 癌細胞A549 的增生,是經由癌細胞的 ROS 增加,促使細胞壞死(圖 7-2)。
圖7-1 大黃酚影響細胞週期的路徑圖
圖7-2 大黃酚影響細胞壞死的路徑圖
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