- 學位論文
β-山竹果素抑制子宮頸癌轉移能力之機制研究
Research on the mechanism of β-mangostin inhibits the metastatic power of cervical cancer cells.
摘要
β-Mangostin是一種自山竹果中萃取出的天然植化物，已證實對許多種癌症均具有抗發炎和抗癌的能力，在這項研究中目的在於探討β-Mangostin能否抑制子宮頸癌HeLa和SiHa細胞的轉移能力並對其分子機制進行研究。利用MTT分析法、細胞聚落形成試驗、流式細胞儀來了解β-Mangostin對子宮頸癌細胞是否具有毒性，結果發現β-Mangostin並不會影響人類子宮頸癌HeLa和SiHa細胞株的細胞活性與細胞週期分布；然而進行體外細胞遷移與細胞侵襲試驗發現β-Mangostin劑量依賴性地抑制HeLa和SiHa細胞的移動與侵襲能力；更進一步利用qRT-PCR、西方墨點法發現β-Mangostin抑制了HeLa和SiHa細胞中integrin αv和β3的表達，同時β-Mangostin也抑制了JNK蛋白的表達；進行β-Mangostin和JNK抑制劑（JNKi）合併使用於體外細胞遷移與細胞侵襲試驗，結果顯示兩者合併使用時會產生協同作用，抑制了HeLa細胞的移動和侵襲能力。綜合以上結果證明β-Mangostin抑制了integrin αv和β3的表現並抑制了JNK路徑的活化，進而抑制了子宮頸癌細胞的侵襲和轉移能力，這些發現也表明自山竹果中萃取出的天然植化物β-Mangostin也許可做為治療子宮頸癌的潛在抗轉移藥物。
並列摘要
β-Mangostin is a natural phytochemical extracted from mangosteen, which has been proven to have anti-inflammatory and anti-cancer capabilities for many types of cancer. The purpose of this study is to investigate whether β-Mangostin can inhibit the metastatic ability of HeLa and SiHa cells (cervical cancer cell lines) and to study its molecular mechanism. By using MTT assay, cell colony formation and flow cytometry to understand whether β-Mangostin is toxic to cervical cancer cells. We found that β-Mangostin did not affect the cell activity and the distribution of cell cycle in HeLa and SiHa cells. However, in vitro cell migration and invasion assays we found that β-Mangostin dose-dependently inhibited the migration and invasion of HeLa and SiHa cells. Further studies with qRT-PCR and Western blot, we found that β-Mangostin inhibited the expression of integrin αv and β3 in HeLa and SiHa cells, and β-Mangostin also inhibited the expression of JNK protein. A combination of β-Mangostin and JNK inhibitor (JNKi) used in in vitro cell migration and invasion assays showed a synergistic effect inhibiting the migration and invasion abilities of HeLa cells. Our results prove that β-Mangostin inhibits the expression of integrin αv and β3 and also inhibits the activation of JNK pathway, thereby inhibiting the invasion and metastasis abilities of cervical cancer cells. These findings indicate that the natural phytochemical β-Mangostin extracted from mangosteen fruit may be used as a potential anti-metastatic target drug for the treatment of cervical cancer.