PMID- 22275271
OWN - NLM
STAT- MEDLINE
DCOM- 20120921
LR  - 20211203
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 113
IP  - 6
DP  - 2012 Jun
TI  - Inhibition of IGF-IR increases chemosensitivity in human colorectal cancer cells 
      through MRP-2 promoter suppression.
PG  - 2086-97
LID - 10.1002/jcb.24080 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Shen, Ke
AU  - Shen K
AD  - State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of 
      Chemical Biology, School of Pharmacy, East China University of Science and 
      Technology, #268, 130 Meilong Road, Shanghai 200237, PR China.
FAU - Cui, Daling
AU  - Cui D
FAU - Sun, Liyun
AU  - Sun L
FAU - Lu, Yanhua
AU  - Lu Y
FAU - Han, Mingquan
AU  - Han M
FAU - Liu, Jianwen
AU  - Liu J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (ABCC2 protein, human)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Multidrug Resistance-Associated Protein 2)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Colorectal Neoplasms/drug therapy/*metabolism/pathology
MH  - Drug Resistance, Multiple/genetics
MH  - Drug Resistance, Neoplasm/genetics
MH  - Humans
MH  - Multidrug Resistance-Associated Protein 2
MH  - Multidrug Resistance-Associated Proteins/*genetics/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering
MH  - Receptor, IGF Type 1/antagonists & inhibitors/genetics/*metabolism
MH  - Signal Transduction
EDAT- 2012/01/26 06:00
MHDA- 2012/09/22 06:00
CRDT- 2012/01/26 06:00
PHST- 2012/01/26 06:00 [entrez]
PHST- 2012/01/26 06:00 [pubmed]
PHST- 2012/09/22 06:00 [medline]
AID - 10.1002/jcb.24080 [doi]
PST - ppublish
SO  - J Cell Biochem. 2012 Jun;113(6):2086-97. doi: 10.1002/jcb.24080.