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國立成功大學「邁向頂尖大學計畫」
延攬優秀人才工作報告表
NCKU’s “Aim for the Top University Project”
Work Report Form for Distinguished Scholars
□續聘continuation of employment ■離職resignation
受聘者姓名
Name of the Employee 郭育汝 □男 ■女
Male Female
聘 期 Period of Employment
From 107 年(y) 01 月(m) 01 日(d) To 107 年(y) 02 月(m) 28 日(d) 研究或教學或科技研發與
管理計畫名稱 The project title of research,
teaching, technology development and management
利用整合蛋白拮抗劑與天然物 發展抗癌藥物
計畫主持人
（申請單位主管）
Project Investigator (Head of Department/Center)
莊偉哲
補助延聘編號
Grant Number HUA107-3-7-053
一、 研究、教學、科技研發與管理工作全程經過概述。（由受聘人填寫）
Please summarize the entire research, teaching, or science and technology R&D and management work process (To be completed by the employee)
Previously results have showed that the integrin αvβ3-specific (ARLDDL) and αvβx and α5β1-specific (KG and KG-P) disintegrins have been designed successfully. In this project, we analyzed the integrin distribution in different HCC and HSC cells and determined the inhibition of cell adhesion of HCC cells using those integrin-specific disintegrins.
I. Integrin expression profiles of HCC cell lines and hepatic stellate cells (HSC)
Figure 1. Integrin distribution in hepatoma cells and hepatic stellate cells.
The solid peak represents the isotype IgG. The open peak represents the fluorescence intensity of integrin, which means the integrin expression level. Integrins αv and β1 were highly expressed in all of the hepatoma cells. On the other hand, the expression level of other integrins exhibited different patterns.
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Figure 2. Integrin expression in hepatoma cells and hepatic stellate cells.
Integrins αv and β1 were highly expressed in all of the hepatoma cells, and expression levels of integrins α5β1, αvβ3, αvβ5, αvβ6, and α2β1 on HCC cell lines were very different. In contrast, integrin expression levels on HSC were very low. These results suggested that integrins αv and β1 might be important for HCC therapy.
II. Inhibition of hepatoma cell adhesion by disintegrins
Rho, KG and KG-P significantly inhibited the adhesion of hepatoma cells (HuH7, Hep3B, and HepG2) to fibronectin and vitronectin, and exhibited higher activity in inhibiting the adhesion to vitronectin. In contrast, ARLDDL weakly inhibited hepatoma cells adhesion to fibronectin and vitronectin due to its lower integrins α5β1 and αvβ5 inhibitory activities. Because Rho has higher integrins αvβ3 and αvβ5 inhibitory activity than KG and KG-P, it exhibited highest activity in inhibiting cell adhesion to vitronectin. Interestingly, we found that integrins-specific disintegrins weakly inhibited PLC cell adhesions to fibronectin and to vitronectin because integrins α5β1 and αvβ5 were highly expressed in PLC cells. These findings were consistent with previous reports that hepatoma cell
adhesions to fibronectin and to vitronectin are mainly regulated by integrin α5β1, and integrins αvβ1 and αvβ5, respectively (Nejjari et al., 2002).
Table 1. The inhibition ability of integrin-specific disintegrins to binding to fibronectin
The value was represented as means ± standard error of mean (the numbers of independent experiments).
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Table 1. The inhibition ability of integrin-specific disintegrins to binding to vitronectin
The value was represented as means ± standard error of mean (the numbers of independent experiments).
II. Inhibition of hepatoma cell migration by disintegrins
The migratory activity of different hepatoma cell lines was tested (Figure 3). The HuH7 cells showed the greater migration ability than others. In addition, the hepatoma cell line that expressed the HBx protein would enhance the migratory activity. Further, the hepatoma cell lines were treated with different disintegrins (Rho, ARLDDL, KG and KG-P) and assessed the cell migration (Table 3). The values represented the IC50 of integrin antagonists for inhibiting hepatoma cell migration. The
αvβx-specific disintegrins (KG and KG-P) could significantly inhibited the migration of hepatoma cell with the IC50 values ranging from 4 to 40 nM.
Figure 3. Comparison of the migration activity of different hepatoma cell lines.
HuH7 was the best in migration ability than others. Having HBx protein increased the migration activity of Hep3B.
Table 3. The inhibition of hepatoma cell migration by disintegrins
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二、研究或教學或科技研發與管理成效評估（由計畫主持人或單位主管填寫）
Please evaluate the performance of research, teaching or science and technology R&D and management Work: (To be completed by Project Investigator or Head of Department/Center)
(1)是否達到延攬預期目標？
Has the expected goal of recruitment been achieved?
受聘人利用整合蛋白拮抗劑與天然物發展抗肝癌藥物之研究，達預期目標，未來可供實驗室 繼續進一步探討。
(2)研究或教學或科技研發與管理的方法、專業知識及進度如何？
What are the methods, professional knowledge, and progress of the research, teaching, or R&D and management work?
受聘人對於瞭解整合蛋白拮抗劑、發展拮抗劑與天然物發展抗肝癌藥物的機制與未來可行性 之探討有達到期望之進度，未來可繼續聘用執行研究目標。
(3)受延攬人之研究或教學或科技研發與管理成果對該計畫(或貴單位)助益如何？
How have the research, teaching, or R&D and management results of the employed person given benefit to the project (or your unit)?
受聘人在此期間對該計畫進行專業學術研究，對於其個人及受聘單位均有所助益。
(4)受延攬人於補助期間對貴單位或國內相關學術科技領域助益如何？
How has the employed person, during his or her term of employment, benefited your unit or the relevant domestic academic field?
受聘人在此聘期內的結果可供實驗室對於拮抗劑與發展抗肝癌藥物的領域繼續深入探討，其 對國內相關學術科技領域及未來醫學也有助益。
(5)具體工作績效或研究或教學或科技研發與管理成果：
Please describe the specific work performance, or the results of research, teaching, or R&D and management work:
受聘人在此期間對於整合蛋白拮抗劑發展為抗肝癌藥物的範疇有達成一定的成果，其工作結 果分析了在不同時期的肝癌細胞與正常細胞之間整合蛋白的分佈狀況，同時證明了我們的去整合 蛋白對於肝癌細胞的轉移及貼附擁有很好的抑制能力。這些成果對於未來發展有效的抗肝癌藥物 是一大幫助。
(6)是否續聘受聘人? Will you continue hiring the employed person? □續聘Yes ■不續聘No
※ 此報告表篇幅以三～四頁為原則。This report form should be limited to 3-4 pages in principle.
※ 此表格可上延攬優秀人才成果報告繳交說明網頁下載。
※ This report form can be downloaded in http://scholar.lib.ncku.edu.tw/explain/
