文献类型：期刊文献

英文题名：Inhibition of IGF-IR increases chemosensitivity in human colorectal cancer cells through MRP-2 promoter suppression

作者：Shen, Ke[2,3];Cui, Daling[2,3];Sun, Liyun[2,3];Lu, Yanhua[2,3];Han, Mingquan[1];Liu, Jianwen[2,3]

机构：[1]Tongji Univ, Shanghai Pulm Hosp, Sch Med, Shanghai 200433, Peoples R China;[2]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Sch Pharm, Shanghai 200237, Peoples R China;[3]E China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2012

卷号：113

期号：6

起止页码：2086

外文期刊名：JOURNAL OF CELLULAR BIOCHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000302613100028)】；

基金：Grant sponsor: Fundamental Research Funds for the Central Universities; Grant sponsor: Shanghai Leading Academic Discipline Project; Grant number: B507; Grant sponsor: 111 Project; Grant number: B07023.

语种：英文

外文关键词：INSULIN-LIKE GROWTH FACTOR TYPE I; MULTIDRUG-RESISTANCE; COLORECTAL CANCER; RNA INTERFERENCE; MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2

摘要：The emergence of multidrug resistance (MDR) in cancer cells has made many of the currently available chemotherapeutic agents ineffective. However, the mechanism involved in mediating this effect is not yet fully understood. Here, we found the overexpression of type I insulin-like growth factor receptor (IGF-IR) in established colorectal MDR cells. Specific siRNA of IGF-IR decreases cell proliferation, exert synergistic effect with anticancer drugs. The downstream signaling of IGF-IR, PI3K/AKT pathway, was altered upon IGF-IR silencing. The expression of multidrug-resistance-associated protein 2 (MRP-2) was suppressed due to the nuclear translocation of nuclear factor-like 2 (Nrf2). Then the intracellular drug concentration was increased and the drug-resistant phenotype was reversed. Our findings improve current understanding of the biology of IGF-IR and MDR and have significant therapeutic implications on colorectal MDR cancer. J. Cell. Biochem. 113: 20862097, 2012. (C) 2012 Wiley Periodicals, Inc.