- 學位論文
探討α-山竹酮素抑制人類腎臟癌細胞轉移之研究
Study on the molecular mechanism of α-mangostin inhibits metastasis on human renal cell carcinoma
摘要
α-山竹酮素(α-mangostin)廣泛存在山竹果皮中，屬於藤黃屬。先前研究報導指出，α-mangostin具有抗菌、抗腫瘤及抗發炎的功效，然而α-mangostin對於人類腎臟癌細胞的轉移機轉仍然未知。本研究主要目的是探討α-mangostin對於腎臟癌細胞移動和侵襲之分子機制。我們利用MTT試驗證實隨著α-mangostin濃度增加不會抑制人類正常腎小管細胞HK2以及人類腎臟癌(786O和A498)細胞生長和細胞週期。我們利用細胞移動及侵襲試驗證明隨著α-mangostin濃度增加明顯抑制786O細胞的移動和侵襲能力，並伴隨抑制MMP-9活性、蛋白量以及mRNA的表現。為了瞭解α-mangostin抑制細胞移動和侵襲之分子機制，我們證實α-mangostin抑制MEK和ERK磷酸化，但不影響p38 和JNK磷酸化。利用MEK抑制劑(U0126)與α-mangostin共同處理證實會明顯抑制MEK/ERK活化、MMP-9表現，進而抑制細胞的移動和侵襲作用。因此，本研究證實α-mangostin可能當作抗腎臟癌細胞之抗癌藥物，主要途徑是透過抑制MEK/ERK和MMP-9表現。
並列摘要
Alpha-mangostin, an effective component in Garcinia mangostana Linn, is a tree found in South East Asia, and its pericarps have been used as traditional medicine. Recent studies revealed that α-mangostin exhibited a variety of biological activities containing anti-inflammatory, anti-bacterial, and anti-cancer effects. However, its effect on human renal cancer cells remains unclear. This study aimed to investigate the roles of α-mangostin in migration and invasion of human renal cancer cells and its possible molecular mechanism. In the present study, we found that α-mangostin did not affect cell growth in human proximal tubule epithelial HK-2 cell line and human kidney cancer 786O and A498 cell lines. α-mangostin treatment inhibited the migration and invasion of 786O cells via inhibiting the enzymatic activities and protein levels of MMP-9, not affect MMP-2 by using a gelatin zymography assay and western blot analyses, as well as the mRNA levels of MMP-9 could also suppressed by α-mangostin. To understand the molecular mechanism of α-mangostin inhibit cell migration and invasion, we found that α-mangostin inhibited the phosphorylation of ERK1/2 and MEK1/2 , the treatment of MEK inhibitor U0126 significantly reduced the α-mangostin inhibited MMP-9 expression, MEK/ERK activation, migration and invasion of 786O cells. Therefore, this study to suggest that α-mangostin might be an anti-metastatic agent against renal cancer cells through the inhibition of MEK/ERK activation and MMP-9 expression.