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Inhibition of IGF‐IR increases chemosensitivity in human colorectal cancer cells through MRP‐2 promoter suppression
Author(s) -
Shen Ke,
Cui Daling,
Sun Liyun,
Lu Yanhua,
Han Mingquan,
Liu Jianwen
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24080
Subject(s) - multiple drug resistance , pi3k/akt/mtor pathway , cancer research , gene silencing , colorectal cancer , protein kinase b , growth factor , intracellular , cancer cell , cell growth , signal transduction , cancer , insulin like growth factor , drug resistance , biology , chemistry , pharmacology , receptor , microbiology and biotechnology , medicine , biochemistry , genetics , gene
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: 2086–2097, 2012. © 2012 Wiley Periodicals, Inc.