紫杉醇是一種抗微小管的藥劑，它可以促使細胞循環周期停滯在G2/M的時期，進而導致細胞走向細胞凋亡的路徑。在臨床化療中，紫杉醇已被廣範的利用在許多的癌症當中，像是乳癌、卵巢癌以及頭頸部癌症。但是，紫杉醇導致人類頭頸部癌症進行細胞凋亡的機制到目前尚有爭議。因此本實驗主要在探討紫杉醇誘導人類頭頸部癌症細胞株細胞凋亡之現象及是否會有caspase以及絲裂原活化蛋白激酶(mitogen- activated protein kinase, MAPK)參與在其中。研究發現，紫杉醇(50 nM)可以導致FaDu及KOSC-3腫瘤細胞的形態改變，並且在48小時的處理後可促使細胞死亡率達到百分之五十以上。藉由細胞流體儀的測定，紫杉醇確實可以導致細胞循環停滯在G2/M時期，進而使去氧核糖核酸套數少於雙套的細胞數增加(這是細胞進行細胞凋亡的一個特徵)。並且發現紫杉醇會活化細胞中的caspase-7, -8和 -9並使poly (ADP-ribose) polymerases (PARP)失去活性。而caspases的活化以及PARP被切割的量是會隨著紫杉醇處理的時間增加而增加。此結果顯示紫杉醇是藉由活化細胞凋亡的機制而導致人類頭頸部腫瘤細胞株死亡。當加入caspase的抑制劑(z-VAD-fmk)後，可以有效的降低紫杉醇導致的細胞死亡量。研究中也發現絲裂原活化蛋白激酶(MAPK)家族中的ERK活性也有隨著紫杉醇處理時間增加而有上升的趨勢。然而，絲裂原活化蛋白激酶(MAPK)家族中的另一成員，JNK並不會因紫杉醇的作用而被活化。總結之，紫杉醇誘導人類頭頸部FaDu及KOSC-3腫瘤細胞凋亡的機制有caspase的參與及ERK活化的現象，而JNK的活化路徑則不參與其中。

　　Paclitaxel, an anti-microtubule agent, can make cell cycle arrest in the G2/M phase and then induces cell apoptosis. Paclitaxel is clinically used to therapy various tumor types, such as breast cancer, ovarian cancer and head and neck cancer. However, the effect and the mechanism of paclitaxel-induced apoptosis in human head and neck cancers remain elusive. In the present study, paclitaxel-induced human head and neck tumor cell lines, FaDu and KOSC-3, cell death was investigated and the caspases and mitogen-activated protein kinase (MAPK) activities related to apoptosis were also determined. Results illustrated that paclitaxel (50 nM) caused morphological changes in both FaDu and KOSC-3 cells after 24 or 48 h treatments, and cell viability decreased around 50%. In flow-cytometry analysis, paclitaxel significantly increased G2/M phase accumulation in FaDu and KOSC-3 cells and then hypodiploid DNA cell number increased, indicating that paclitaxel could induce DNA fragmentation, a characteristic of apoptosis. My study also showed that activation of caspases-7, -8 and -9 and the cleavage of poly (ADP-ribose) polymerases (PARP) could be detected by Western blotting analysis in time-dependent manners. In addition, general caspase inhibitor, z-VAD-fmk, reduced paclitaxel-induced cell death, providing further evidence that paclitaxel-induced human head and neck cancer cell death was via the apoptosis pathway. Furthermore, my study also showed that ERK was activated in paclitaxel-induced apoptosis in FaDu and KOSC-3 cells. However, JNK was not activated by paclitaxel in both cell lines. Taken together, paclitaxel can induce apoptosis in human head and neck cancer cells by activating caspase and MAPK signal pathways.

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