The mechanisms of lung cancer cells against TRAIL-induced apoptosis

• Main Authors: Chao-weu Jiang, 江肇偉
• Other Authors: Wen-Jun Wu, Ph. D.
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/50463501088827750796

碩士 === 中山醫學大學 === 毒理學研究所 === 91 === TRAIL is a new proapoptotic cytokine. It is believed that TRAIL can selectively kill cancer cells but not normal cells. Moreover, TRAIL induces apoptosis through binding its two proapoptotic receptors, DR4 and DR5. The TRAIL signaling pathway is modulated by two antiapoptotic TRAIL decoy receptors, DcR1 nd DcR2. Previous results of the sensitivity of NSCLC to TRAIL—indued apoptosis show that H460 and A549 are the most sensitive to TRAIL；H1299 and H1355 are the most resistance to TRAIL. First of all, we investigate the relationship between the expression of antiapoptotic proteins and proapoptotic proteins on TRAIL-induced apoptosis. We found that the expression of antiapoptotic proteins and proapoptotic proteins to TRAIL-induced apoptosis have no apparent correlation. And then, we also investigate the basal NF-κB activity of the most sensitive and resistance lung cancer cell lines. Finally, we blocked NF-κB activity by an inhibitor of proteasome activity, MG132；and inhibitor of IκB phosphorylation, BAY 11-7085 and Parthenolide. We found that MG132 and Parthenolide can enhance TRAIL—indued apoptosis, except BAY 11-7085. These data sugesst that NF-κB may play an important role in TRAIL-induced apoptosis. This research may provide a molecular approach targeting NF-κB for promising therapy in cilinical.