評估GRB2SH2的合成胜肽抑制劑對人類乳癌細胞MCF-7與MDA-MB453的生物活性

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Title:	評估GRB2SH2的合成胜肽抑制劑對人類乳癌細胞MCF-7與MDA-MB453的生物活性
Other Titles:	Effects of synthetic peptide inhibitors of GRB2 SH2 on human breast cancer cells
Authors:	陳盟凱 Chen, Meng-Kai
Contributors:	龍鳳娣,鄭啟清 Lung, Feng-Di;Jeng, Kee-Ching 東海大學化學系
Keywords:	設計胜肽;人類乳癌細胞株;細胞存活率;細胞毒性;細胞週期;細胞凋亡 design peptide, human breast cancer cell line, cell viability, cell cytotoxicity, cele cycle,apoptosis
Date:	2007
Issue Date:	2011-03-21T06:33:28Z (UTC)
Abstract:	生長因子受體連接蛋白質之SH2 區塊(Src homology 2 domains)在細胞內的致病機轉訊息傳遞途徑中，對於細胞增生與分化，扮演著非常重要的角色。因此以Grb2 SH2 區塊為標靶的抑制劑成為具有潛力發展的抗癌藥物的研究標的。本實驗室最近利用表面膜漿共振技術的生物感測器發展出一系列對Grb2 SH2 區塊具有高親和力的設計胜肽。在此篇論文中，將對Grb2 SH2 區塊具有高親和力的胜肽對不同的人類乳癌細胞株進行生物活性測試。將不同濃度的設計胜肽(Fmoc-Glu-Tyr-Aib-Asn-NH2 and Arg-Gly-Asp-Glu-Tyr-Aib-Asn-Arg-Gly- Asp-NH2)處理人類乳癌細胞株，利用MTT 與LDH kit 測試細胞存活率與細胞毒性。並且利用流式細胞技術進行設計胜肽對人類乳癌細胞之細胞週期與細胞凋亡的相關實驗。實驗結果顯示，設計胜肽對人類乳癌細胞株MCF-7 與MDA-MB-453 之細胞存活率的IC50 分別為45.72 M與47.43 M，並且細胞毒性隨著胜肽濃度與處理時間的增加，而具有顯著差異表現。經過胜肽處理後的人類乳癌細胞株之細胞週期，亦隨著胜肽濃度的增加，sub-G1期也隨之增加。因此証實小分子設計胜肽可以使人類乳癌細胞株MCF-7 與MDA-MB-453 走向死亡。而胜肽對於人類乳癌細胞內分子傳遞路徑機轉，尚待進一步研究。 The growth factor receptor-bound protein Src homology 2 (Grb2-SH2) plays an important role in the oncogenic Ras signaling pathway, which involves in cell proliferation and differentiation. Therefore, the Grb2-SH2 inhibitors become a potential target for developing anticancer agents. Recently, we discovered peptides with high affinity for Grb2 SH2 domain which was detected by SPR-biosensor technology. In this study, we investigated the biological activities of designed peptides (Fmoc-Glu-Tyr-Aib-Asn-NH2 and Arg-Gly-Asp-Glu- Tyr-Aib-Asn-Arg-Gly-Asp-NH2) in different human breast cancer cell lines. The breast cancer cells of MCF-7 and MDA-MB-453 were treated with various concentrations of designed peptides, the cell viability and cell cytotoxicity were determined using the cell proliferation kit (3-[4, 5-dimethylth -iazol-2-yl]-2,5-diphenyltetrazolium bromide, MTT) and cell cytotoxicity kit (LDH kit). Effects of peptides on the cell cycle progression of cancer cells and apoptosis were studied by flow cytometry. Results demonstrated that our lead peptide (Arg-Gly-Asp-Glu- Tyr-Aib-Asn-Arg-Gly-Asp-NH2) exhibits anti-proliferative effects on MCF-7 and MDA-MB-453 with the IC50 of 64 ?M and 50 ?M, respectively. The cell cytotoxicity and percentage of sub-G1 in cell cycle of both cancer cells were increased when the cells were treated with higher concentration of peptides or treated for prolonged time.
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