Linked Life Data

20876799

Source:http://linkedlifedata.com/resource/pubmed/id/20876799

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2010-10-15
pubmed:abstractText
Apatinib, a small-molecule multitargeted tyrosine kinase inhibitor, is in phase III clinical trial for the treatment of patients with non-small-cell lung cancer and gastric cancer in China. In this study, we determined the effect of apatinib on the interaction of specific antineoplastic compounds with P-glycoprotein (ABCB1), multidrug resistance protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2). Our results showed that apatinib significantly enhanced the cytotoxicity of ABCB1 or ABCG2 substrate drugs in KBv200, MCF-7/adr, and HEK293/ABCB1 cells overexpressing ABCB1 and in S1-M1-80, MCF-7/FLV1000, and HEK293/ABCG2-R2 cells overexpressing ABCG2 (wild-type). In contrast, apatinib did not alter the cytotoxicity of specific substrates in the parental cells and cells overexpressing ABCC1. Apatinib significantly increased the intracellular accumulation of rhodamine 123 and doxorubicin in the multidrug resistance (MDR) cells. Furthermore, apatinib significantly inhibited the photoaffinity labeling of both ABCB1 and ABCG2 with [(125)I]iodoarylazidoprazosin in a concentration-dependent manner. The ATPase activity of both ABCB1 and ABCG2 was significantly increased by apatinib. However, apatinib, at a concentration that produced a reversal of MDR, did not significantly alter the ABCB1 or ABCG2 protein or mRNA expression levels or the phosphorylation of AKT and extracellular signal-regulated kinase 1/2 (ERK1/2). Importantly, apatinib significantly enhanced the effect of paclitaxel against the ABCB1-resistant KBv200 cancer cell xenografts in nude mice. In conclusion, apatinib reverses ABCB1- and ABCG2-mediated MDR by inhibiting their transport function, but not by blocking the AKT or ERK1/2 pathway or downregulating ABCB1 or ABCG2 expression. Apatinib may be useful in circumventing MDR to other conventional antineoplastic drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1538-7445
pubmed:author
pubmed:copyrightInfo
©2010 AACR.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7981-91
pubmed:dateRevised
2011-10-17
pubmed:meshHeading
pubmed-meshheading:20876799-ATP-Binding Cassette Transporters, pubmed-meshheading:20876799-Adenosine Triphosphatases, pubmed-meshheading:20876799-Animals, pubmed-meshheading:20876799-Breast Neoplasms, pubmed-meshheading:20876799-Cell Line, Tumor, pubmed-meshheading:20876799-Cell Survival, pubmed-meshheading:20876799-Doxorubicin, pubmed-meshheading:20876799-Drug Resistance, Multiple, pubmed-meshheading:20876799-Enzyme Inhibitors, pubmed-meshheading:20876799-Female, pubmed-meshheading:20876799-Humans, pubmed-meshheading:20876799-Mice, pubmed-meshheading:20876799-Mice, Inbred BALB C, pubmed-meshheading:20876799-Mice, Nude, pubmed-meshheading:20876799-P-Glycoprotein, pubmed-meshheading:20876799-Protein-Tyrosine Kinases, pubmed-meshheading:20876799-Pyridines, pubmed-meshheading:20876799-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20876799-Transplantation, Heterologous
pubmed:year
2010
pubmed:articleTitle
Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters.
pubmed:affiliation
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural