Linked Life Data

19125612

Source:http://linkedlifedata.com/resource/pubmed/id/19125612

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-2-2
pubmed:abstractText
Mammalian target of rapamycin (mTOR) is a regulator of cell growth and proliferation and its activity is altered in many human cancers. The main objective of this study was to evaluate in vitro and in vivo targeting of mTOR by photodynamic therapy (PDT), a treatment modality for cancer. The amphiphilic endolysosomal localizing photosensitizer AlPcS(2a) and the p53 mutated rapamycin-resistant colon adenocarcinoma cell line WiDr were used as models. AlPcS(2a)-PDT downregulated the levels of Ser(2448) phosphorylated mTOR (p-mTOR), total mTOR and phosphorylation of ribosomal S6 (p-S6) immediately after light exposure in a dose-dependent manner, indicating a direct targeting of the mTOR signaling network. Low-dose PDT attenuated the level of p-mTOR in a transient manner; approximately 35% reduction of p-mTOR was obtained 5 min after a LD(35) PDT dose, but returned to the basal level 24 h later. Treatment with the mTOR inhibitor rapamycin reduced the p-mTOR level by 25% after 4-24 h of incubation. Combination treatment of rapamycin and PDT in vitro resulted in synergistic cytotoxic effects when rapamycin was administered after PDT. However, antagonistic effects were obtained when rapamycin was incubated both before and after PDT. In vivo, activated mTOR in the WiDr-xenografts was downregulated by 35 and 75% 5 min and 24 h post PDT respectively as measured by immunoblotting. In contrast to untreated tumors where p-mTOR expression was found throughout the tumors, immunohistochemical staining revealed only expression of p-mTOR in the rim of the tumor at 24 and 48 h post PDT. In conclusion, AlPcS(2a)-PDT is a novel mTOR-targeted cancer therapy. Rapamycin synergistically enhances the cytotoxicity of PDT only when administered post light exposure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1543-8384
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
255-64
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:articleTitle
Photodynamic therapy targets the mTOR signaling network in vitro and in vivo.
pubmed:affiliation
Department of Radiation Biology, Norwegian Radium Hospital, Oslo, Norway.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't