Snail1 downstream target and drug resistance

• Main Authors: Ching-Jung Chu, 朱慶榮
• Other Authors: Kou-Juey Wu
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/55740114060434068504

碩士 === 國立陽明大學 === 生化暨分子生物研究所 === 97 === Chemotherapy resistance is still a major problem for the cancer patients treated with chemotherapeutic drugs. However, the molecule mechanism of chemotherapy resistance is unclear. We previously demonstrated that the head and neck cancer patients with high expression level of Snail1 have poor prognosis. Therefore, we want to discuss the relationship between Snail1 and chemotherapy resistance. The results show that ERCC1, TUBB3 are downregulated and the non-small-cell-lung cancer cell lines (H1299) sensitize to cisplatin and paclitaxel when the expression of Snail1 is decreased. The overexpression of NBS1 in head and neck cancer cell lines (FADU-NBS1) can induce the expression of Snail1, ERCC1 and TUBB3. ERCC1 or TUBB3 is knockdown in NBS1 overexpression head and neck cancer cell lines by siRNA can increase the sensitivity of the cancer cell lines to cisplatin or paclitaxel. Besides, we also find Snail1 can regulate the promoter region of NDRG1, a tumor suppressor gene, and affect the expression of NDRG1. These results indicate Snail1 may mediate the chemotherapy resistance through regulation of ERCC1, TUBB3 and NDRG1 in cancer cell lines.