蟲草素亦稱為3'-脫氧腺苷，為腺苷之類似物。蟲草素為冬蟲夏草中主要的活性化合物，已被發現其具有增強免疫力、抑制腫瘤生長及血管新生等功用。在我們先前的研究中表明，蟲草素透過調控整聯蛋白及黏著斑激酶 (integrin/FAK) 之訊息傳遞路徑降低肝癌細胞之上皮-間質轉化 (EMT) 。黏著斑激酶 (FAK) 為一種調節血管發育之細胞基質激酶，其在細胞中扮演著重要的角色，包括調節內皮細胞 (EC) 之貼附、遷移、增生及存活等。然而，蟲草素對於內皮細胞之血管新生作用仍是未知的。於本研究中，我們發現蟲草素抑制內皮細胞中黏著斑激酶之活性及Y397位點之磷酸化，進而降低細胞遷移及增生。於共聚焦顯微鏡檢查中顯示，蟲草素顯著的減少黏著斑激酶之表現及數量。此外，蟲草素亦增加了p53及p21蛋白質之表達，從而導致G1細胞週期停滯。最後，在體外及體內模型中皆顯示出蟲草素抑制血管新生。我們透過體外血管新生分析發現處理蟲草素的實驗組抑制了體外血管管腔之生成，另一方面在實驗鼠中亦發現蟲草素抑制了血管新生。綜合以上結果表明，蟲草素可能透過抑制黏著斑激酶之表達及增加p53和p21蛋白質表現量來抑制內皮細胞中之血管生成、細胞遷移和增殖。我們的結果顯示，蟲草素可能具有用於預防血管新生的潛在治療或輔助化合物之潛力。

Cordycepin, known as 3’-deoxyadenosine, is an analogue of adenosine. Cordycepin is the major active compound in Dong Chong Xia Cao which has been found to enhance immune function and inhibit tumor growth and angiogenesis formation. Our previous study indicated that cordycepin reduced the epithelial-mesenchymal transition (EMT) via the integrin/FAK signaling in hepatocellular carcinoma. Focal adhesion kinase (FAK) is a cytoplasmic kinase that regulates vascular development, including the endothelial cell (EC) adhesion, migration, proliferation, and survival. However, the effect of cordycepin on angiogenesis formation is still underdetermined. In this study, we found that cordycepin inhibits activation of FAK and phosphorylates FAK at the position of Y397 in ECs leading to suppression of cell migration and proliferation. Confocal microscopy indicated that cordycepin significantly reduced FAK expression and decreased focal adhesion number of ECs. In addition, cordycepin increased the protein expression of p53 and p21 which causes the G1 cell-cycle arrest. Finally, the treatment of cordycepin inhibited the tube formation and angiogenesis in the in vitro and in vivo model. These results suggest that cordycepin may inhibit angiogenesis, cell migration and proliferation in ECs via suppressing FAK expression and increasing p53 and p21 expression. As a result, cordycepin may be a potential therapeutic or supplementary compound used for preventing angiogenesis.

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