PCK3145衍生肽在大腸直腸癌中的結構 - 抗增殖活性關係之研究

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题名:	PCK3145衍生肽在大腸直腸癌中的結構 - 抗增殖活性關係之研究
其它题名:	Studies of the Structure-Antiproliferative Activity Relationships of PCK3145-derived Peptides in Colorectal Cancer
作者:	劉品秀 LIU,PIN-XIU
贡献者:	龍鳳娣 LUNG,FENG-DI 化學系
关键词:	細胞訊息傳遞路徑;PCK3145;人類結腸癌細胞;抗癌胜肽 cellular signaling pathways;PCK3145;colon cancer cells;ACPs
日期:	2019
上传时间:	2019-12-16T02:22:24Z (UTC)
摘要:	細胞訊息傳遞路徑會影響細胞之生理作用，使細胞適應外界的改變。據文獻指出前列腺分泌蛋白94 (PSP94) 是人類精液中最主要的成分之一，其已被確定可作為前列腺癌的獨立診斷與預後的生物標記物，並可能作為前列腺腫瘤的抑制劑與治療藥物。其中被激活的 ERK 細胞傳遞路徑參與諸多細胞活動，包括細胞增殖和存活。而活化的 ERK 會將許多基質(其他激酶和轉錄因子)磷酸化，使下游路徑執行與細胞週期分化、蛋白質轉譯和避免細胞死亡相關的程序。而 PCK3145 是一段擷取自 PSP94 蛋白的胜肽序列，已被證實可抑制前列腺癌、乳癌及結腸癌腫瘤的生長，並可能是透過磷酸化 MEK 與 ERK1/2 的途徑達成功效。本實驗室選擇此 PCK3145 為依據，設計出一系列的短胜肽命名為 PJ系列，並探討其結構與抗增殖活性之關係。設計之胜肽應用固相胜肽合成法（SPPS）來合成，再以逆相-高效能液相層析儀（RP-HPLC）進行純化並以基質輔助雷射脫附游離飛行時間質譜儀（MALDI-TOF MS）來鑑定純化之胜肽。將目標胜肽進行生物活性測試（MTT assay）來評估對人類結腸癌細胞（SW480及HT-29）的抗增殖能力。根據實驗結果顯示，截短的 PCK3145 之衍生肽 PJ 系列對結腸癌細胞並沒有顯著的抑制效果，推測PCK3145原序列之結構在抗癌細胞增殖活性中可能有一定的影響。 Cellular signaling pathways affect the physiological function of cells and enable them to respond to changes in the environment. According to the literature, prostate secretory protein 94 (PSP94) is one of the most important components in human semen and has been identified as an independent biomarker for the diagnosis and prognosis of prostate cancer and may be used as prostate tumor inhibitors and treatment drugs. Activation of the ERK pathway regulates many cellular activities, including cell proliferation and survival. Activated ERK phosphorylates many substrates, including other kinases and transcription factors, performing processes related to cell cycle differentiation, protein translation, and cell death avoidance. PCK3145, a peptide sequence derived from PSP94, has been shown to inhibit tumor growth in prostate, breast and colon cancers, possibly through phosphorylation of MEK and ERK 1/2. Based on PCK3145, we designed a series of peptides named PJ series, which were applied to study the structure-antiproliferative activity relationships . The peptide was synthesized by solid phase peptide synthesis (SPPS), purified by reversed phase high performance liquid chromatography (RP-HPLC) and identified by Matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). MTT assay was used to evaluate the anti-proliferation of human colon cancer cells (SW480 and HT-29), and the experimental data were analyzed. According to the experimental results, the PJ series did not significantly inhibit the proliferation of colon cancer cells, suggesting that PCK3145 original structural amino acid sequence plays an important role in the anti-proliferation of cancer cells.
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