Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/22784
標題: 蘆薈大黃素對舌咽癌細胞株之凋亡和侵犯機制的影響
The Effects of Aloe-Emodin on Apoptosis and Invasion of the Pharyngeal Squamous Carcinoma Cell Line
作者: 張兆嶔
Chang, Chao-Chin
關鍵字: 蘆薈大黃素
aloe emodin
舌咽癌細胞
出版社: 生命科學系所
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摘要: 雖然有證據證明蘆薈大黃素具有成為抗癌藥物的潛力,但蘆薈大黃素引起人類舌咽癌細胞株凋亡的機制卻尚未瞭解。在本篇研究中首先證實了蘆薈大黃素能夠抑制舌咽癌細胞株的增生並且誘發其凋亡,在蘆薈大黃素所引發的細胞凋亡中可以清楚的觀察到細胞核的濃縮與染色體的裂解,蘆薈大黃素所引起的細胞凋亡伴隨著Bax表現量的上升和Bcl-XL表現量的下降,而Bcl-2的表現量則無顯著變化。在以蘆薈大黃素處理過的舌咽癌細胞中還觀察到caspase-3活性的提高,粒線體膜電位下降,造成cytochrome c和AIF自粒線體轉位至細胞質,並且提高了細胞質中ROS和鈣離子的含量。這些結果說明了蘆薈大黃素在舌咽癌細胞中經由粒線體所調控的途徑誘發舌咽癌細胞進行細胞凋亡;另外,它還能藉由降低MAPK訊息傳導路徑中上游重要的蛋白質的表現量,如Grb2和SOS1,使得下游的轉錄因子調控的基因,如MMP-9,的表現量下降,進一步造成癌細胞移轉的能力下降。以上結果說明了蘆薈大黃素可能作為一種有效治療舌咽癌細胞的抗癌藥物。
Although there are evidences showing that aloe-emodin might be a potential anticancer drug, but the mechanisms that involved in its action on the induction of apoptosis in human pharyngeal squamous carcinoma(PSC)cells are remained to defined. In the present study, we first demonstrated that aloe-emodin could inhibit proliferation and induce apoptosis in PSC cells. Aloe-emodin-induced apoptosis was clearly verified by the appearance of nuclear condensation and DNA fragmentation. Apoptosis induced by aloe-emodin was accompanied by the up-regulation of Bax and down-regulation of Bcl-XL, but no effect on the level of Bcl-2. A significant increase in caspase-3 activity was observed in aloe-emodin treated PSC cells. Moreover, we found that aloe-emodin induced the loss of mitochondrial membrane potential(MMP), the release of cytochrome c and apoptosis-inducing factor(AIF)from mitochondria to cytosol. And also resulted in an elevation of reactive oxygen species (ROS) and increase calcium (Ca++) level in cytosol. In addition to inducing apoptosis, aloe-emodin inhibited the expressions of important proteins in Ras-MAPK signaling pathway, Grb2 and SOS1, and the genes regulated by the signaling pathway were suppressed. As the genes regulated by Ras-MAPK signaling pathway, MMP-9 and VEGF, were down-regulated, the invasion activity of cancer cells was suppressed. These results suggest that aloe-emodin induced apoptosis and inhibited invasion in PSC cells were mediated through mitochondria dependent and Ras-MAPK pathways. It implies the possibility that aloe-emodin could be a useful anticancer agent for treatment of PSC.
URI: http://hdl.handle.net/11455/22784
其他識別: U0005-2608200811503000
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2608200811503000
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