Nucleophosmin/B23-binding peptide regulates the increase in expression of p53, Bax and has potent anti-tumor activity

• Main Authors: Chan Hui-Chia, 詹蕙嘉
• Other Authors: Yung Yat-Ming
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/52006616201774791048

碩士 === 長庚大學 === 基礎醫學研究所 === 91 === Abstract Nucleophosmin/B23 (NPM/B23) is a major nucleolar phosphoprotein, which is more abundant in tumor and proliferating cells than in normal cells. We have previous reported that NPM/B23 over-expressed cells decreased the response to apoptosis or differentiation. Excess of nucleophosmin/B23 is an important cause of cancer and not just a consequence. Recent studies have shown the protein B23 forms a specific complex with the human immunodeficiency virus type 1 (HIV 1) Rev protein. Furthermore it is reported that Rev-NLS peptide, a synthetic peptide containing the NLS sequence of HIV-1 Rev protein has a high affinity to B23. In our recent findings shows that the clinic tissue of recurrent bladder cancer have more abundant NPM/B23 than primary bladder cancer. MGH-U1 is a human transitional bladder tumor cell line. And MGH-U1R is a established by culturing MGH-U1 in increasing concentrations of doxorubicin. MGH-U1R is 70 times more resistant to doxorubicin than MGH-U1. Here we show that Rev peptide can potentiate the induced inhibition of growth and apoptosis in both MGH-U1 and MGH-U1R. Moreover MGH-U1R is only 2~3 times resistance to Rev peptide (have high affinity with NPM/B23) than MGH-U1. Rev peptide can decrease the tumor volume of bladder cancer in nude mice. Furthermore the tumor suppressor p53 and bax were increased in protein level during Rev peptide induces bladder cancer cells to apoptosis.