目前研究顯示口腔癌有cyclooxygenase-2 (COX-2)過度表現的現象，但是COX-2在口腔癌上扮演的角色目前仍不清楚。本研究在測試Sulindac，一個具有化學預防作用的非類固醇抗發炎藥和綠茶萃取物對於由N-methyl-N-benzylnitrosamine (MBN)誘發倉鼠產生口腔癌的抑制作用。先以1% MBN （每週三次）共8週誘發倉鼠產生口腔癌後，再給予含320 ppm sulindac的飼料或含0.2 %的綠茶水共9週，給藥的同時仍持續處理MBN。在給MBN 17週後犧牲倉鼠，結果顯示先誘發口腔癌後再給予藥物的動物模式，Sulindac明顯的抑制腫瘤的數目( p<0.01)及腫瘤的大小（p<0.05），而綠茶萃取物與對照組比較僅抑制了口腔癌的腫瘤數目（p<0.05）。在口腔組織免疫化學試驗，未給MBN對照組的COX-2量很少並且分佈平均，但是在MBN所誘發的鱗狀上皮細胞癌的腫瘤上則有大量的COX-2表現。以西方墨點法來分析COX-2蛋白質的表現，對照組（以 propylene glycol處理），口腔表皮組織COX-2蛋白質的含量非常少幾乎沒有，然而COX-2在鱗狀上皮細胞癌的腫瘤上增加約4倍。結果亦顯示由 MBN誘發產生的鱗狀上皮細胞癌，其組織中PGE2值較對照組明顯增高。綜合以上結果，清楚顯示COX-2與口腔癌發生有關，並且非類固醇抗發炎藥可有效抑制由MBN誘導倉鼠產生口腔鱗狀上皮細胞癌的作用。

Recent studies have demonstrated the overexpression of cyclooxygenase-2 (COX-2) in oral cancer, but the role of COX-2 in oral carcinogenesis remains unclear. This study is designed to test whether sulindac, a potential chemopreventive non-steroidal anti-inflammatory drug (NSAID), and green tea extract has potential to reduce the N-methyl-N-benzylnitrosamine (MBN)-induced tumorigenesis in hamster buccal pouch. Sulindac was administered in the diet (320 ppm) and green tea extract was given in the drinking water (0.2 %) to hamsters that were pretreated with 1 % MBN (3 times a week) for 8 weeks. The sulindac and green tea extract treatment continued for another 9 weeks while the MBN treatment continued. The late treatment of sulindac caused significant reduction in both the multiplicity ( p<0.01) and size ( p<0.05) of tumors than the controls. On the other hand, 0.2% green tea extract in drinking water only reduced the number ( p<0.05) of oral cancer lesions than the controls. By using immunohistochemistry, COX-2 was diffusely stained in control pouch, but strongly present in the MBN-induced tumor cells. Western blot analysis revealed COX-2 protein was barely detectable in the propylene glycol-treated controls, whereas it was increased 4-fold in MBN-induced squamous cell carcinomas (SCCs). The results also indicated the PGE2 level was significantly increased in MBN-induced SCCs than the controls. These results clearly indicate that COX-2 is involved in oral carcinogenesis and NSAID has potential against the postinitiation develeopment of SCCs in MBN-induced hamster oral cancers.

中文摘要
英文摘要
壹、 緒論
第一章 口腔癌
第一節 口腔癌之流行病學
第二節 口腔癌之分子致癌機轉
第三節 口腔癌的治療
第二章 花生四烯酸的代謝
第一節 簡介
第二節 cyclooxygenase的介紹
第三章 COX-2在癌症上扮演的角色
第一節 簡介
第二節 COX-2與大腸癌
第三節 COX-2與口腔癌
第四節 COX-2與其他癌症
第四章 PGE2在癌症上扮演的角色
第五章 Sulindac的介紹
第一節 簡介
第二節 Sulindac與癌症
第六章 綠茶的介紹
第一節 簡介
第二節 綠茶的成分
第三節 綠茶與癌症
第七章 實驗設計
第一節 實驗動物－倉鼠
第二節 MBN的介紹
第三節 實驗模式
貳、 實驗材料
參、 實驗方法
肆、 實驗結果
伍、 討論
陸、 結論
柒、 參考文獻
捌、 實驗圖表

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