- 學位論文
生育酚相關蛋白與紫檀芪於人類乳腺癌細胞之抗癌作用的研究
Studies on Anticarcinogenic Effects of Tocopherol-Associated Protein (TAP) and Pterostilbene in Human Breast Cancer Cell
摘要
乳癌是女性最常見的惡性腫瘤，並且具有年齡特異的發病特性。在過去的十年中，許多研究已經證明天然的維生素E，α-生育酚(α-tocopherol)，具有抗癌的特性。在人體血清、肝、腦，和前列腺組織中，α-生育酚相關蛋白（α-Tocopherol-associated protein, TAP）被證實為α-生育酚之最主要和最活躍的結合蛋白質。本研究以即時性－聚合酶連鎖反應方式，從93例乳癌樣本的正常和癌症組織的配對中，發現降低TAP的表現，與人類表皮生長因子受體2 （Human epidermal growth factor receptor 2, HER2）表現，乳癌分期，及淋巴結分期有顯著的相關性。細胞存活率實驗指出，α-生育酚琥珀酸酯（α-tocopheryl succinate, α-TOS），一種α-生育酚的衍生物，提高了小紅莓doxorubicin對細胞敏感度，並導致乳腺癌細胞活力的降低。我們還發現，紫檀芪（Pterostilbene, PS），膳食中藍莓的抗氧化成分，能協同α-TOS使乳腺癌細胞的生長減緩。令人驚喜的是，在動物模式中，給予小鼠PS和高劑量的維生素E飲食，發現乳腺腫瘤生長受到抑制。綜合以上結果，證明維生素E和PS作為補充劑可同時提供乳癌的預防和臨床治療效果。
並列摘要
Breast cancer is the most common malignancy among women and has an age-specific incidence profile. Over the last decade, many studies have demonstrated the anticancer activity of?悈-tocopherol, the main and most active form of natural vitamin E. α-Tocopherol-associated protein (TAP) was found to be one of the major α-tocopherol binding proteins in human serum and in liver, brain, and prostate tissues. In this study, we found that reduced TAP expression was significantly correlated with Her2 receptor expression, breast cancer stage and nodal stage in paired normal and cancerous breast tissue samples from 93 patients using real-time PCR analysis. A cell viability assay showed that α-tocopheryl succinate (α-TOS), a synthetic derivative of α-tocopherol, enhanced the cells’sensitivity to doxorubicin and resulted in a reduction in cell viability in breast cancers. We also found Pterostilbene (PS), a natural dietary antioxidant component of blueberries, has demonstrated the synergic decrease on breast cancer cell growth effects by the combination of α-TOS exposure. Surprisingly, in animal model, treatment of PS and high level Vitamin E diet also induced breast tumor growth inhibition. Taken together, these data suggest that Vitamin E and PS as supplements may provide both breast tumor preventative and therapeutic benefits in clinic.