Linked Life Data

17828283

Source:http://linkedlifedata.com/resource/pubmed/id/17828283

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-12
pubmed:abstractText
FUS1 is a novel tumor suppressor gene located in the human chromosome 3p21.3 region. We previously showed that restoration of FUS1 function in 3p21.3-deficient human non-small-cell lung cancer (NSCLC) cells significantly inhibited tumor cell growth in vitro and in vivo. In this study, we evaluated the combined effects of the tumor suppressor FUS1 and the chemotherapeutic drug cisplatin on tumor cell growth and apoptosis induction in NSCLC cells, and explored the molecular mechanism of their mutual action. Exogenous expression of FUS1 by nanoparticle-mediated gene transfer sensitized the response of NSCLC cells to cisplatin, resulting in a 4- to 6-fold increase in tumor-suppressing activity. A systemic treatment with a combination of FUS1-nanoparticles and cisplatin in a human H322 lung cancer orthotopic xenograft mouse model dramatically enhanced the therapeutic efficacy of cisplatin. We also found that the FUS1-enhanced chemosensitivity is associated with the downregulation of MDM2, accumulation of p53 and activation of the Apaf-1-dependent apoptosis pathway. Our results demonstrated an important role of FUS1 in modulating chemosensitivity of lung cancer cells, and suggested that a proper combination of molecular therapeutics such as the proapoptotic tumor suppressor FUS1 and the conventional chemotherapeutic drugs such as cisplatin may be an efficient treatment strategy for human lung cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-5500
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29-39
pubmed:meshHeading
pubmed-meshheading:17828283-Animals, pubmed-meshheading:17828283-Antineoplastic Agents, pubmed-meshheading:17828283-Apoptotic Protease-Activating Factor 1, pubmed-meshheading:17828283-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:17828283-Cell Line, Tumor, pubmed-meshheading:17828283-Chromosomes, Human, Pair 3, pubmed-meshheading:17828283-Cisplatin, pubmed-meshheading:17828283-Down-Regulation, pubmed-meshheading:17828283-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17828283-Gene Therapy, pubmed-meshheading:17828283-Gene Transfer Techniques, pubmed-meshheading:17828283-Humans, pubmed-meshheading:17828283-Lung Neoplasms, pubmed-meshheading:17828283-Mice, pubmed-meshheading:17828283-Nanoparticles, pubmed-meshheading:17828283-Proto-Oncogene Proteins c-mdm2, pubmed-meshheading:17828283-Tumor Suppressor Protein p53, pubmed-meshheading:17828283-Tumor Suppressor Proteins, pubmed-meshheading:17828283-Xenograft Model Antitumor Assays
pubmed:year
2008
pubmed:articleTitle
Enhancement of antitumor activity of cisplatin in human lung cancer cells by tumor suppressor FUS1.
pubmed:affiliation
Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural