基金項目：國家自然科學基金(81101496, 81172003);高等學校博士學科點專項科研基金新教師類資助課題基金(20113234120009) 作者簡介：白小明(1979),女,講師,主要研究方向:PGE2促進腫瘤細胞遷移與轉移的機制 通信聯系人：冷靜(1954),男,教授,主要研究方向:PGE2促進腫瘤細胞生長與擴散的機制.
摘要：目的：闡明前列腺素E2(prostaglandin E2, PGE2)通過EP1受體活化肝癌細胞Huh-7中粘著斑激酶進而促進細胞粘附與遷移的機制。方法：用PGE2、EP1受體激動劑（17-phenyltrinor Prostaglandin E2，17-PT-PGE2）、EP1受體抑制劑SC-19220等處理Huh-7細胞，通過Western blot方法檢測粘著斑激酶磷酸化水平。用WST檢驗細胞粘附水平，用transwell小室檢驗細胞遷移水平。結果：17-PT-PGE2 (3 μM) 處理Huh-7細胞使粘著斑激酶FAK Y397磷酸化水平增高2倍，并使細胞粘附率與遷移率分別增高60%與40%。HEK293細胞中過表達EP1受體使FAK磷酸化水平明顯增高，而EP1受體抑制劑sc-19220阻斷PGE2介導的FAK磷酸化。結論：PGE2可通過EP1受體上調Huh-7細胞中FAK磷酸化水平，進而促進細胞粘附與遷移。
Prostaglandin E2 EP1 Receptor Promotes Hepatocellular Carcinoma Cells Migration via regulating FAK 20 Phosphorylation
BAI Xiaoming, LENG Jing
(Department of Pathology, Nanjing Medical University, Nanjing 210029)
Abstract: The prostaglandin E2 (PGE2) EP1 receptor has been implicated in hepatocellular carcinoma (HCC) cell invasion. However, little is known about the mechanisms of EP1 25 receptor-mediated cell adhesion and migration. We previously showed that PGE2 promotes cell adhesion and migration by activating focal adhesion kinase (FAK). This current study was designed to clarify the association between the EP1 receptor and FAK activation in HCC cells and to investigate the related signal pathway. The effects of PGE2, EP1 agonist 17-phenyl trinor-PGE2 (17-PT-PGE2) and EP1 antagonist inhibitor (sc-19220) on FAK activation were investigated by 30 treatment of Huh-7 cells. Phosphorylation of FAK Y397 was investigated by Western blotting. Cell adhesion and migration were analyzed by WST and transwell assays, respectively. The results showed that 17-PT-PGE2 (3 μM) increased FAK Y397 phosphorylation by more than 2-fold and promoted cell adhesion and migration in Huh-7 cells. Meanwhile, in transfected 293 cells, expression of the EP1 receptor was confirmed to upregulate FAK phosphorylation, while the EP1 receptor antagonist sc-19220 decreased PGE2-mediated FAK activation. Our study suggests that the PGE2 EP1 receptor regulates FAK phosphorylation, which may regulate adhesion and migration in HCC.
Key words: Pathology; EP1 receptor; Focal Adhesion Kinase; Cell Adhesion; Migration; Hepatocellular Carcinoma
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