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Antiproliferative Properties of Sphingosine 1-Phosphate in Human Prostate CancerPC-3 Cell Line

S1P抑制人類前列腺癌細胞PC-3的生長

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摘要


惡性腫瘤是國人十大死因中的第一名,前列腺癌症更是好發於成年男性。水解磷酸脂對於癌症細胞生長與轉移的影響,近年來逐漸在不同細胞間被釐清。Lysophosphatidic acid(LPA)與Sphingosine 1-phosphate (S1P)爲兩種常見的水解磷酸脂,LPA已知能刺激人類前列腺癌細胞PC-3的生長。本研究首次發現S1P在PC-3細胞上有與LPA截然不同的反應,S1P會抑制細胞週期進行,使細胞停滯在G1期。同時,S1P也造成細胞內actin的重組,形成stress fiber與cortical ring,使細胞圓化。可能藉此改變細胞與細胞外基質間刺激細胞分裂生長的訊息傳遞,進而造成細胞死亡。除此之外,S1P也透過未知的機制,調控細胞中水解磷酸脂特異性受器基因的表現。這些反應下的訊息傳遞與調控機制,是接下來有待釐清的課題。

並列摘要


Lysophosphatidic acid (LPA) and Sphingosine 1-phosphate (S1P) are potent growth factors with diverse biological activities. There are many observations suggest that lysophospholipids are important on the regulation of cancer cell proliferation. LPA activates ERK pathway and induce proliferation of human prostate cancer cell line PC-3. However, the effect of S1P on prostate cancer is still poorly understood. In this study, we found that S1P caused cell cycle arrest in G1 phase and inhibit cell proliferation. S1P also induced morphological changes of cells and actin reorganization within 30 mins. In addition, S1P regulated the Edg receptors expression profile of PC-3 cells by itself. In conclusion, S1P might change the cell-ECM interaction through cytoskeleton reorganization and therefore influence cell proliferation in a time-dependent manner.

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