Linked Life Data

20126979

Source:http://linkedlifedata.com/resource/pubmed/id/20126979

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-2-3
pubmed:abstractText
Docetaxel, a member of the taxane family, induces antitumor effects in patients with advanced gastric cancer. However, toxicity at therapeutic doses can be severe, resulting in discontinuation of therapy. It is possible that dose reduction due to adverse events may decrease the cytotoxic efficacy of docetaxel. PSK, a protein-bound polysaccharide, has been used as a chemoimmunotherapy agent in the treatment of cancer in Asia for over 30 years. In the present study, we investigated the enhancing effects of PSK on the cytotoxicity of docetaxel in human gastric cancer through non-immunological actions both in vitro and in vivo. The sensitization effects of PSK on docetaxel were evaluated by MTT assay using human gastric cancer cell lines in vitro. In addition, to elucidate the molecular mechanism, we analyzed the activation of NF-kappaB and the subsequent production of the antiapoptotic molecule survivin in combined treatment with docetaxel and PSK. Accordingly, TMK-1 xenograft growth in SCID mouse was used to evaluate the in vivo efficacy, and the survivin expression in xenografts was also investigated by immunohistochemistry. In vitro, PSK enhanced docetaxel-induced growth inhibition in TMK-1 cells. The docetaxel-induced NF-kappaB activation was inhibited by adding PSK in a dose-dependent manner. Furthermore, the expression of survivin, which is transcriptionally regulated by NF-kappaB, was also inhibited by treatment with PSK. In SCID mouse, PSK significantly inhibited growth of TMK-1 subcutaneous xenografts in combination with low-dose docetaxel, and decreased the docetaxel-induced survivin expression in TMK-1 xenografts. Our data suggest that PSK enhanced the efficacy of docetaxel against human gastric cancer both in vitro and in vivo, at least in part, by downregulating NF-kappaB activation and survivin expression induced by low-dose docetaxel.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1791-2423
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
593-600
pubmed:meshHeading
pubmed-meshheading:20126979-Animals, pubmed-meshheading:20126979-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:20126979-Apoptosis, pubmed-meshheading:20126979-Cell Line, Tumor, pubmed-meshheading:20126979-Dose-Response Relationship, Drug, pubmed-meshheading:20126979-Female, pubmed-meshheading:20126979-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20126979-Humans, pubmed-meshheading:20126979-Inhibitor of Apoptosis Proteins, pubmed-meshheading:20126979-Mice, pubmed-meshheading:20126979-Mice, SCID, pubmed-meshheading:20126979-Microtubule-Associated Proteins, pubmed-meshheading:20126979-NF-kappa B, pubmed-meshheading:20126979-Neoplasm Transplantation, pubmed-meshheading:20126979-Proteoglycans, pubmed-meshheading:20126979-Repressor Proteins, pubmed-meshheading:20126979-Stomach Neoplasms, pubmed-meshheading:20126979-Taxoids
pubmed:year
2010
pubmed:articleTitle
PSK enhances the efficacy of docetaxel in human gastric cancer cells through inhibition of nuclear factor-kappaB activation and survivin expression.
pubmed:affiliation
Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan. junkino0416@gmail.co.jp
pubmed:publicationType
Journal Article