Engineered Escherichia coli as Targeted Drug Delivery System for HER2 Positive Cancers

• Main Authors: Shao-Yu Huang, 黃紹宇
• Other Authors: 劉俊吉
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/94310822145780021975

碩士 === 國立中興大學 === 基因體暨生物資訊學研究所 === 104 === Many researchers believe that bacteria have the potential of precise targeting to cancer cells, which is a great advantage that traditional chemotherapies still lack of. In order to make cancer-killing bacteria into reality, researchers must fulfill two requirements: cancer targeting ability and cancer-killing toxin production. The target we chose is HER2, the member of the human epidermal growth factor receptor family, which is a transmembrane protein that regulates the signals of cell progression, survival, proliferation and motility. Several cancer lines would amplify HER2 gene and lead to abnormal cell growth. As a result, HER2 overexpression often associate with aggressive progression, increased recurrence and metastasis. To locate HER2 protein, researchers have discovered a combinatorial protein called “Affibody”, which was derived from staphylococcal protein A mutant library. Affibody is able to bind HER2 with high affinity. Researchers also found that if E. coli displayed affibody on the cell surface, the bacteria would invade HER2-positive cancer cell lines efficiently. As for the toxin, the ideal choice would be the azurin, which is originally a redox protein that participated in the electron transfer during denitrification by Pseudomonas aeruginosa. Azurin have the preference to selectively internalize into cancer cells while sparing normal cells around, stabilize p53 protein structure, and thus trigger the cell apoptosis pathway. Our research combines affibody and azurin to cure HER2/neu positive cancer cell lines, such as breast cancer BT-474.