人類表皮調節素(human epiregulin)為表皮細胞生長因子(Epidermal growth factor, EGF)的家族成員之一，過去的研究發現它具有促進表皮細胞生長的功能，也因此吸引了腫瘤醫學研究者的目光，自1995年人類表皮調節素首次被證明其存在以來的許多文獻顯示其表現量在胃癌細胞中受到明顯的抑制，而且分析罹患大腸癌的病患後發現其表現量與病患的存活率有顯著的相關性，人類表皮調節素表現量較高的大腸癌患者的存活率相對較高，這個發現與實驗室先前的病患組織分析研究一致，本研究利用大腸桿菌大量表現重組人類表皮調節素並加以純化，改良本實驗室學長所建立的復性反應條件以及復性後的目標重組蛋白構型純化的方法，達到產率大幅提升、製備程序精簡的成果。本實驗室之前的研究中已經證實重組人類表皮調節素具有與A431癌細胞株的表面受體結合之能力，因此本研究選擇A431癌細胞株為細胞活性實驗的對象，並且成功證明此細胞生長確實受到重組人類表皮調節素的抑制(p<0.01)，最後，本研究發現重組人類表皮調節素與用於治療大腸癌患者的標靶藥物Cetuximab抑制A431癌細胞株生長的能力具有加乘性(p<0.05)，並討論是否有發展成合併治療的可能性。

Epiregulin, a member of epidermal growth factor family, plays an important role in colorectal cancer. Previous studies indicated that high expression level of epiregulin was associated with longer overall survival (OS) and progression-free survival (PFS). To test the potential of epiregulin to become a brand-new protein drug, recombinant human epiregulin (rhEREG) was overexpressed in the E.coli expression system and purified via affinity chromatography. Improvement of refolding procedure was required to maximize the yield of the desired conformation of rhEREG. Furthermore, we had discovered a novel method to enhance its purity and simplify the refolding & purification process. Growth inhibition of A431 cell line by rhEREG was examined by cell viability assay (p<0.01). The inhibition reached 35 % when rhEREG concentration was 300 nM. Finally, an enhanced growth inhibition effect of A431 was observed from a combined treatment of rhEREG with cetuximab, a classic IgG antibody used in the colorectal cancer therapy (p<0.05).

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