PMID- 22174910
OWN - NLM
STAT- MEDLINE
DCOM- 20120423
LR  - 20240313
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 12
DP  - 2011
TI  - Antitumor activity of sorafenib in human cancer cell lines with acquired 
      resistance to EGFR and VEGFR tyrosine kinase inhibitors.
PG  - e28841
LID - 10.1371/journal.pone.0028841 [doi]
LID - e28841
AB  - Treatment of non small cell lung cancer (NSCLC) and colorectal cancer (CRC) have 
      substantially changed in the last years with the introduction of epidermal growth 
      factor receptor (EGFR) inhibitors in the clinical practice. The understanding of 
      mechanisms which regulate cells sensitivity to these drugs is necessary for their 
      optimal use.An in vitro model of acquired resistance to two tyrosine kinase 
      inhibitors (TKI) targeting the EGFR, erlotinib and gefitinib, and to a TKI 
      targeting EGFR and VEGFR, vandetanib, was developed by continuously treating the 
      human NSCLC cell line CALU-3 and the human CRC cell line HCT116 with escalating 
      doses of each drug. MTT, western blot analysis, migration, invasion and 
      anchorage-independent colony forming assays were conducted in vitro and 
      experiments with established xenografts in athymic nude mice were performed in 
      vivo in sensitive, wild type (WT) and TKI-resistant CALU-3 and HCT116 cell 
      lines.As compared to WT CALU-3 and HCT116 human cancer cells, TKI-resistant cell 
      lines showed a significant increase in the levels of activated, phosphorylated 
      AKT, MAPK, and of survivin. Considering the role of RAS and RAF as downstream 
      signals of both the EGFR and VEGFR pathways, we treated resistant cells with 
      sorafenib, an inhibitor of C-RAF, B-RAF, c-KIT, FLT-3, RET, VEGFR-2, VEGFR-3, and 
      PDGFR-beta. Sorafenib reduced the activation of MEK and MAPK and caused an 
      inhibition of cell proliferation, invasion, migration, anchorage-independent 
      growth in vitro and of tumor growth in vivo of all TKI-resistant CALU-3 and 
      HCT116 cell lines.These data suggest that resistance to EGFR inhibitors is 
      predominantly driven by the RAS/RAF/MAPK pathway and can be overcame by treatment 
      with sorafenib.
FAU - Morgillo, Floriana
AU  - Morgillo F
AD  - Division of Medical Oncology, Department of Clinical and Experimental Medicine 
      and Surgery F Magrassi e A Lanzara Second University of Naples, Naples, Italy. 
      florianamorgillo@yahoo.it
FAU - Martinelli, Erika
AU  - Martinelli E
FAU - Troiani, Teresa
AU  - Troiani T
FAU - Orditura, Michele
AU  - Orditura M
FAU - De Vita, Ferdinando
AU  - De Vita F
FAU - Ciardiello, Fortunato
AU  - Ciardiello F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20111209
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzenesulfonates)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
SB  - IM
ECI - PLoS One. 2019 Apr 11;14(4):e0215109. PMID: 30973909
RIN - PLoS One. 2024 Jan 25;19(1):e0298013. PMID: 38271443
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Benzenesulfonates/*pharmacology
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - ErbB Receptors/*antagonists & inhibitors/metabolism
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Mice
MH  - Neoplasm Invasiveness
MH  - Niacinamide/analogs & derivatives
MH  - Phenylurea Compounds
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Pyridines/*pharmacology
MH  - Receptors, Vascular Endothelial Growth Factor/*antagonists & 
      inhibitors/metabolism
MH  - Signal Transduction/drug effects
MH  - Sorafenib
MH  - Xenograft Model Antitumor Assays
PMC - PMC3235154
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/12/17 06:00
MHDA- 2012/04/24 06:00
PMCR- 2011/12/09
CRDT- 2011/12/17 06:00
PHST- 2011/05/25 00:00 [received]
PHST- 2011/11/16 00:00 [accepted]
PHST- 2011/12/17 06:00 [entrez]
PHST- 2011/12/17 06:00 [pubmed]
PHST- 2012/04/24 06:00 [medline]
PHST- 2011/12/09 00:00 [pmc-release]
AID - PONE-D-11-09426 [pii]
AID - 10.1371/journal.pone.0028841 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(12):e28841. doi: 10.1371/journal.pone.0028841. Epub 2011 Dec 9.