PMID- 21406185
OWN - NLM
STAT- MEDLINE
DCOM- 20110705
LR  - 20181201
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 81
IP  - 11
DP  - 2011 Jun 1
TI  - Suppression of Stat3 activity sensitizes gefitinib-resistant non small cell lung 
      cancer cells.
PG  - 1263-70
LID - 10.1016/j.bcp.2011.03.003 [doi]
AB  - Epidermal growth factor receptor (EGFR) is a proven therapeutic target to treat a 
      small subset of non small cell lung cancer (NSCLC) harboring activating mutations 
      within the EGFR gene. However, many NSCLC patients are not sensitive to EGFR 
      inhibitors, suggesting that other factors are implicated in survival of NSCLC 
      cells. Signal transducers and activators of transcription 3 (Stat3) function as 
      transcription factor to mediate cell survival and differentiation and the 
      dysregulation of Stat3 has been discovered in a number of cancers. In this study, 
      we found that a small molecule, reactivation of p53 and induction of tumor cell 
      apoptosis (RITA), showed anti-cancer activity against gefitinib-resistant H1650 
      cells through a p53-independent pathway. Stat3 suppression by RITA attracted our 
      attention to investigate the role of Stat3 in sustaining survival of H1650 cells. 
      Pharmacological and genetic approaches were employed to down-regulate Stat3 in 
      H1650 cells. WP1066, a known Stat3 inhibitor, was shown to exhibit inhibitory 
      effect on the growth of H1650 cells. Meanwhile, apoptosis activation by 
      siRNA-mediated down-regulation of Stat3 in H1650 cells provides more direct 
      evidence for the involvement of Stat3 in viability maintenance of H1650 cells. 
      Moreover, as a novel identified Stat3 inhibitor, RITA increased doxorubicin 
      sensitivity of H1650 cells in vitro and in vivo, suggesting that doxorubicin 
      accompanied with Stat3 inhibitors may be considered as an alternative strategy to 
      treat NSCLC patients who have inherent resistance to doxorubicin. Overall, our 
      observations reveal that targeting Stat3 may be an effective treatment for 
      certain NSCLC cells with oncogenic addition to Stat3.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Chiu, Huan-Chih
AU  - Chiu HC
AD  - Institute of Biotechnology and Pharmaceutical Research, National Health Research 
      Institutes, Miaoli, Taiwan.
FAU - Chou, Ding-Li
AU  - Chou DL
FAU - Huang, Chin-Ting
AU  - Huang CT
FAU - Lin, Wen-Hsing
AU  - Lin WH
FAU - Lien, Tzu-Wen
AU  - Lien TW
FAU - Yen, Kuei-Jung
AU  - Yen KJ
FAU - Hsu, John T-A
AU  - Hsu JT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110322
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Pyridines)
RN  - 0 (Quinazolines)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tyrphostins)
RN  - 0 (WP1066)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Blotting, Western
MH  - Carcinoma, Non-Small-Cell Lung/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm
MH  - Flow Cytometry
MH  - Gefitinib
MH  - Humans
MH  - Lung Neoplasms/metabolism/*pathology
MH  - Pyridines/pharmacology
MH  - Quinazolines/*pharmacology
MH  - RNA Interference
MH  - STAT3 Transcription Factor/*antagonists & inhibitors/metabolism
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Tyrphostins/pharmacology
EDAT- 2011/03/17 06:00
MHDA- 2011/07/06 06:00
CRDT- 2011/03/17 06:00
PHST- 2011/01/28 00:00 [received]
PHST- 2011/03/02 00:00 [revised]
PHST- 2011/03/03 00:00 [accepted]
PHST- 2011/03/17 06:00 [entrez]
PHST- 2011/03/17 06:00 [pubmed]
PHST- 2011/07/06 06:00 [medline]
AID - S0006-2952(11)00148-1 [pii]
AID - 10.1016/j.bcp.2011.03.003 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2011 Jun 1;81(11):1263-70. doi: 10.1016/j.bcp.2011.03.003. 
      Epub 2011 Mar 22.