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  • 學位論文

本土丹參萃取物對口腔癌腫瘤之治療潛力評估

Studies on the anti-cancer potential of Danshen extract in oral cancer

指導教授 : 蔡婉琪
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摘要


癌症是國人死亡原因之首,即使在醫藥發達的現今,癌症的死亡率依然居高不下。其中約有九成的口腔癌屬於惡性程度且轉移能力極高的鱗狀上皮細胞癌。目前臨床上所使用的藥物多為利用抑制DNA合成、細胞分裂與促進凋亡等能力而達到抗癌的效果。研究指出傳統東洋醫學中治療心血管疾病的丹參(Salvia miltiorrhiza)主要成分 tanshinone 與 salvianolic acid 用以治療乳癌、肝癌、血癌、卵巢癌等皆有不錯的效果。除了能夠有效抑制癌細胞生長,同時也能促使癌細胞的凋亡。本研究利用一系列體內及體外實驗探討丹參對於口腔癌的治療潛力。由結果得知丹參確實能夠抑制口腔癌細胞株 OC-2 與HSC-3 的生長,同時也發現較高濃度的丹參萃取液顯著增加癌細胞中caspase-3 的表現量。進一步分析 Bcl-2 family、inhibitor of apoptosis(IAP) family 與 endoplasmic reticulum (ER) stress 等細胞凋亡途徑之相關蛋白,發現其中抗凋亡蛋白 survivin 的表現量隨著丹參萃取液濃度增加而明顯下降,顯示丹參萃取液藉由調控 IAP family 而達到誘導細胞凋亡的效果。同時,在動物實驗中,連續 35 天經由腹腔注射給予丹參萃取液後,注射50 mg/kg 藥物的組別,其腫瘤抑制率為 25 %,而 100 mg/kg 的組別則有 68 %的腫瘤抑制效果,結果證實丹參萃取液 確實能夠有效的透過促進細胞凋亡使得腫瘤成長受到抑制。

關鍵字

丹參 口腔癌

並列摘要


Oral cancer is a global health problem with increasing incidence and mortality rates, and it has become the 4th ranking cancer among all sites of cancer in Taiwanese male. In the recent study, tanshinone and salvianolic acid, which are the major components of Danshen, had great effects on treating breast cancer, hepatocellular carcinoma, promyelocytic leukemia and clear cell carcinoma of the ovary by inhibiting proliferation of cancer cells and promoting the apoptosis. In this study, Danshen extract was used to treat on oral cancer cells OC-2 and HSC-3. The results showed that the Danshen extract could inhibit cancer cells proliferation significantly. The apoptotic protein, caspase-3, also been found that the expression level increased with the rising concentration of the Danshen extract. The apoptosis pathway-related proteins, including Bcl-2 family, inhibitor of apoptosis (IAP) family and endoplasmic reticulum (ER) stress protein were further examined to decipher the targets of Danshan extract. Survivin, an anti-apoptosis protein of IAP family, was markedly inhibited by Danshen extract treatment in a dose-dependent manner. These data suggested that the Danshen extract exerted its apoptosis-inducing effects via targeting on the IAP family, especially on survivin. Furthermore, the growth of HSC-3 tumor xenografts was suppressed by 25% and 68% after treatment with Danshen extract at 50 and 100 mg/kg, respectively, for 35 days. Taken all data together, by inducing apoptosis, Danshen extract showed appreciable effects on inhibiting growth of oral cancer cells in vitro and in vivo.

並列關鍵字

Danshen Oral cancer

參考文獻


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