論文

査読有り
2009年10月

Downregulation of matrix metalloprotease-9 and urokinase plasminogen activator by TX-1877 results in decreased tumor growth and metastasis on xenograft model of rectal cancer

CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • Kotaro Miyake
  • ,
  • Mitsuo Shimada
  • ,
  • Masanori Nishioka
  • ,
  • Koji Sugimoto
  • ,
  • Erdenebulgan Batmunkh
  • ,
  • Yoshihiro Uto
  • ,
  • Hideko Nagasawa
  • ,
  • Hitoshi Hori

64
5
開始ページ
885
終了ページ
892
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00280-009-0937-5
出版者・発行元
SPRINGER

It is well known that hypoxic milieu is the primary cancer environment. Therefore, tumor hypoxia is considered to be a potential therapeutic target. In the present study, we investigated the antitumor and antimetastatic effect of hypoxic cell radiosensitizer, TX-1877 on xenograft model of rectal cancer.
Nude mice bearing subcutaneously or orthotopically implanted human colon cancer cell lines HCT-116 and HT-29 were treated with TX-1877, irradiation or TX-1877 with irradiation. Tumor volume, survival, expression of matrix metalloproteinase (MMP)-2, MMP-7, MMP-9 and urokinase-type plasminogen activator (uPA) and incidence of lymph node metastasis were evaluated in treatment versus control group.
In subcutaneous model, tumor treated with TX-1877 and irradiation showed significant reductions in volume (P < 0.05 vs. control, TX-1877 or irradiation group). Quantitative real-time reverse transcription-PCR and immunohistochemical analysis revealed that TX-1877 significantly inhibited expression of the MMP-9 and uPA. These treatments also inhibited the para-aortic lymph node metastasis, however, did not prolong the survival in orthotopic model.
These data show that the treatment of TX-1877 with irradiation decreased growth of human rectal cancer and, furthermore, suppressed lymph node metastasis.

Web of Science ® 被引用回数 : 9

リンク情報
DOI
https://doi.org/10.1007/s00280-009-0937-5
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19214512
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000269076700004&DestApp=WOS_CPL