Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan 32546, Taiwan.
Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
Int J Mol Sci. 2021 Feb 14;22(4):1902. doi: 10.3390/ijms22041902.
Epidermal growth factor receptor (EGFR) specific therapeutics is of great importance in cancer treatment. Fcy-hEGF fusion protein, composed of yeast cytosine deaminase (Fcy) and human EGF (hEGF), is capable of binding to EGFR and enzymatically convert 5-fluorocytosine (5-FC) to 1000-fold toxic 5-fluorocuracil (5-FU), thereby inhibiting the growth of EGFR-expressing tumor cells. To develop EGFR-specific therapy, Re-liposome-Fcy-hEGF was constructed by insertion of Fcy-hEGF fusion protein onto the surface of liposomes encapsulating of Re. Western blotting, MALDI-TOF, column size exclusion and flow cytometry were used to confirm the conjugation and bio-activity of Re-liposome-Fcy-hEGF. Cell lines with EGFR expression were subjected to treat with Re-liposome-Fcy-hEGF/5-FC in the presence of 5-FC. The Re-liposome-Fcy-hEGF/5-FC revealed a better cytotoxic effect for cancer cells than the treatment of liposome-Fcy-hEGF/5-FC or Re-liposome-Fcy-hEGF alone. The therapeutics has radio- and chemo-toxicity simultaneously and specifically target to EGFR-expression tumor cells, thereby achieving synergistic anticancer activity.
表皮生长因子受体 (EGFR) 特异性治疗在癌症治疗中具有重要意义。Fcy-hEGF 融合蛋白由酵母胞嘧啶脱氨酶 (Fcy) 和人 EGF (hEGF) 组成，能够与 EGFR 结合，并将 5-氟胞嘧啶 (5-FC) 酶促转化为毒性强 1000 倍的 5-氟尿嘧啶 (5-FU)，从而抑制 EGFR 表达的肿瘤细胞生长。为了开发 EGFR 特异性治疗，将 Fcy-hEGF 融合蛋白插入到包裹 Re 的脂质体表面上构建了 Re-liposome-Fcy-hEGF。使用 Western blot、MALDI-TOF、柱尺寸排阻和流式细胞术证实了 Re-liposome-Fcy-hEGF 的缀合和生物活性。用 Re-liposome-Fcy-hEGF/5-FC 处理具有 EGFR 表达的细胞系，同时存在 5-FC。Re-liposome-Fcy-hEGF/5-FC 对癌细胞的细胞毒性作用优于脂质体-Fcy-hEGF/5-FC 或 Re-liposome-Fcy-hEGF 单独处理。该疗法同时具有放射和化学毒性，并特异性靶向 EGFR 表达的肿瘤细胞，从而实现协同抗癌活性。
