探討棉酚抑制口腔癌細胞癌幹性之功效

癌症幹細胞已証實於口腔腫瘤起始、增生、轉移以及抗藥性扮演相當重要的角色。因此針對癌症幹細胞發展標靶療法是目前改善臨床醫學上對於癌症治療的新契機。本研究發現存在於棉花的棉籽及棉根皮中的多酚類物質棉酚於口腔癌症幹細胞具有細胞毒殺作用，對人類正常口腔牙齦角化細胞而言，棉酚在濃度為10μM以下時並沒有顯著的細胞毒性產生。而依隨著棉酚處理濃度上升，口腔癌症幹細胞二次球體形成力下降。我們的研究顯示，棉酚能顯著降低口腔癌症幹細胞標記－乙醛脫氫酶（aldehyde dehydrogenase 1, ALDH1）的活性，棉酚投予之濃度越高，則ALDH1之表現量越低。隨著棉酚劑量上升，其抑制口腔癌症幹細胞之致癌性如遷移、侵襲和群落形成的能力更佳。棉酚處理可明顯抑制口腔癌幹細胞中幹性基因Bmi1 mRNA表現量。口腔癌症幹細胞與一般口腔癌症細胞相較之下，具有更強的傳統化療藥物阻抗性，而細胞存活率實驗棉酚能降低口腔癌症幹細胞對於化療藥物－氟尿嘧啶（5-Fluorouracil, 5-FU）及順鉑(cisplatin)的抗藥性。綜合上述，驗證棉酚可有效抑制口腔癌細胞之癌性及轉移特性之實驗，期待能輔助化學治療藥物之抗癌效果，以提供臨床做為治療口腔癌的基礎。

Relative to remaining the tumor bulk, cancer stem cells (CSCs) are often more tumorigenic, chemo-resistant/radio-resistant, and metastatic in oral cancer. Therefore, development of novel therapeutics targeting CSCs could significantly improve clinical outcome of oral cancer treatment. As gossypol, a natural phenol derived from the cotton plant could suppress cell proliferation of oral sphere-forming CSCs in a dose-dependent manner. The effect of gossypol on normal human oral epithelial cells (SG) revealed that this compound did not have any significant cytotoxicity on these cells. Our data suggested gossypol treatment significantly decrease ALDH1, a marker of oral CSCs, activity in a concentration-dependent manner. Substantial evidence has demonstrated that gossypol dose-dependently inhibited migration, invasion, and colony-forming abilities in oral CSCs. Gossypol dose-dependently inhibited stemness marker Bmi1 expression in oral CSCs. Oral CSCs were more chemo-resistant compared with the parental oral cancer cells. Importantly, cell viability assays showed that gossypol ameliorated the drug resistance of oral CSCs to fluorouracil (5-FU) and cisplatin treatment. Conclusively, the present reports showed that the gossypol effectively suppressed cancer stemnness, chemo-resistant properties of oral CSCs, supporting its clinical application for oral cancer patients treatment.