带有EGF受体干扰序列的γ干扰素新分子抗肿瘤细胞增殖活性的提高

利用基因工程技术,将天然IFN-γ分子的N端132个氨基酸与带有上皮生长因子(EGF)样多肽C端保守序列融合,构建了干扰素重组体IFN-γ132PGIX_(16).其中X_(16)由EGF样多肽C端16个氨基酸组成,PGI为连接肽序列。将此重组体基因插入表达载体pBV220P_RP_L串连启动子下游,转化大肠杆菌DH5α,在cIts857基因的调节下,通过升温诱导表达.表达产物与其母体天然IFN-γ相比,不仅保持了较高的抗病毒活性,抗病毒滴度达530MU/L菌液,而且明显地提高了抗肿瘤细胞增殖活性.在EGF存在的条件下,干扰素重组体的抗鼻咽癌细胞CNE-2增殖活性明显高于其母体分子(p<0.01).提示重组体分子IFN-γ132PGIX_(16)同时具有EGF受体干扰活性.     

A NEW HUMAN INTERFERON-γ MUTANT HARBORING EGF RECEPTOR-INTERFERING SEQUENCE POSSESSES HIGH ANTIPROLIFERATIVE ACTIVITY

An interferon gamma (IFN-γ) mutant gene harboring an additionamal epidermal growth factor (EGF) sequence at its 3' terminal was constructed and highly expressed in E. coli by using pBV220 as a vector. The new fusion protein-lFN-γ-EGF possesses not only high antiviral activity, but also high antiproliferative effect as demonstrated by ~3H-TdR incorporation method using CN Ⅱ ceils which are rich in EGF receptors.