Linked Life Data

12124325

Source:http://linkedlifedata.com/resource/pubmed/id/12124325

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2002-7-18
pubmed:abstractText
Treatment of the human colon cancer cells Hct116 with SN-38 (an active metabolite of CPT-11) resulted in G2 cell cycle arrest without induction of apoptosis. However, subsequent treatment of SN-38-treated Hct116 cells with flavopiridol induced apoptosis. One of the genes markedly up-regulated during cell cycle arrest by SN-38 and suppressed during apoptosis by SN-38 followed by flavopiridol in Hct116 cells is Drg1. We found that Drg1 had profound effects on SN-38 sensitivity. Inhibition of endogenous Drg1 expression in Hct116 cells by stable expression of an antisense (AS) Drg1 cDNA increased the sensitivity of cells to undergo apoptosis by SN-38. Clonogenic and apoptosis assays with AS Drg1-expressing cells showed a 2-fold decrease in the IC50 and a 4-5-fold increase in induction of apoptosis with SN-38. Conversely, the forced expression of Drg1 in SW620 cells increased the resistance of these cells to SN-38-induced apoptosis by 2-5-fold. Moreover, when xenografted in mice, AS Drg1-expressing Hct116 cells were 3-fold more sensitive to CPT-11 as compared with vector transfected Hct116 cells. Similarly, tumors established from Drg1 overexpressing SW620 cells were more resistant to CPT-11 as compared with tumors established from vector-transfected SW620 cells in mice. Taken together, our data suggest that Drg1 is a novel gene that plays a direct role in resistance to CPT-11. Inhibition of Drg1 may provide a new means to increase the sensitivity of colon cancer cells to CPT-11.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3950-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12124325-Animals, pubmed-meshheading:12124325-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:12124325-Apoptosis, pubmed-meshheading:12124325-Camptothecin, pubmed-meshheading:12124325-Colonic Neoplasms, pubmed-meshheading:12124325-DNA, Antisense, pubmed-meshheading:12124325-DNA, Complementary, pubmed-meshheading:12124325-Drug Synergism, pubmed-meshheading:12124325-Flavonoids, pubmed-meshheading:12124325-GTP-Binding Proteins, pubmed-meshheading:12124325-Humans, pubmed-meshheading:12124325-Male, pubmed-meshheading:12124325-Mice, pubmed-meshheading:12124325-Mice, Nude, pubmed-meshheading:12124325-Piperidines, pubmed-meshheading:12124325-Prodrugs, pubmed-meshheading:12124325-Tumor Cells, Cultured, pubmed-meshheading:12124325-Xenograft Model Antitumor Assays
pubmed:year
2002
pubmed:articleTitle
Drg1, a novel target for modulating sensitivity to CPT-11 in colon cancer cells.
pubmed:affiliation
Gastrointestinal Oncology Research Laboratory, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.