探討靈芝萃取物WSG抑制口腔癌細胞與 合併臨床用藥順鉑的功效與機轉 ; A study exploring the efficacy and mechanism of Ganoderma lucidum extract WSG alone or in combination with cisplatin in inhibiting tumor cells in oral cancer

博士 指導教授:陳立昇 共同指導教授:鄭信忠 委員: 陳立昇 委員: 鄭信忠 委員: 李忠興 委員: 黃瓊芳 委員: 林東毅 ; 口腔癌發生速率在我國快速的成長，成為台灣頭頸癌的第一位，對國人的健康造成了莫大的威脅，其中以舌癌發生率最高，目前並沒有專一性的標靶藥物能有效地抑制口腔癌，臨床治療最常見的藥物順鉑往往因嚴重的副作用影響治療意願，而靈芝做為最具有抗癌潛力的抗癌藥物，已被證實能誘發多種癌細胞株死亡，其中取自靈芝（Ganoderma lucidum）的水溶性富含葡萄糖的多醣體WSG對肺癌具有極好的療效，但其針對人類口腔癌的抗癌功能與機制，還需進一步探討。 據本研究顯示，WSG對正常口腔細胞安全無毒殺作用，並改善了順鉑對正常口腔表皮SG細胞的細胞毒性作用，WSG可顯著降低舌癌細胞的存活率及聚落生成。增加了subG1及G2/M期的細胞族群數量，並誘發了細胞凋亡反應，WSG還加強了BAX/Bcl2的比值。研究顯示，WSG降低了EGFR與AKT的磷酸化。此外，在抑制細胞存活率及誘發細胞凋亡上，WSG與順鉑（cisplatin）具有增效效應：更降低了順鉑的半抑制濃度（IC50）。綜上所述，本研究中WSG經由抑制EGFR/AKT軸線及誘發口腔癌細胞凋亡的現象，提供了重要的研究證據，顯示WSG可作為一項值得開發、使用、治療口腔癌治療的天然藥物。 With the rapidly increasing incidence of oral cancer, it has become top 1 cancer among head and neck cancers in Taiwan, thus posing a great threat to the public health. Among oral cancer, tongue cancer has the highest incidence. At present, no target-specific drug products are available exclusively for the inhibition of oral cancer. The most commonly used drug in clinical practice, cisplatin, compromises the treatment intention of patients due to severe side effects. Whereas Ganoderma lucidum, the most promising anti-cancer drug, has been demonstrated to induce the death of tumor cells in a variety of cancer cell lines. The extract from G. lucidum, a water-soluble glucose-rich polysaccharide (WSG), is found to have excellent efficacy in the treatment of lung cancer, but further studies are accessory to evaluate the anti-cancer efficiency and mechanism in the treatment of human oral cancer. As shown in this study, WSG was safe and non-toxic in normal oral cells, which improved the cytotoxic effects of cisplatin on normal oral epidermal SG cells and significantly reduced the viability and colony-forming of tongue tumor cells. It increased the number of the cluster of cells in subG1 and G2/M phases, and induced apoptosis as well as enhanced the ratio of BAX/Bcl2. This study showed that WSG reduced the phosphorylation of EGFR and AKT. In addition, WSG showed a synergistic effect with cisplatin in inhibiting the viability and inducing the apoptosis of ...