Research article summary (published 13 May 2007):

Involvement of aminopeptidase N in enhanced chemosensitivity to paclitaxel in ovarian carcinoma in vitro and in vivo.

Full Abstract

Aminopeptidase N (APN/CD13), a 150-kDa metalloproteinase, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression in several human malignancies. In the current study, we investigated the role of APN/CD13 in paclitaxel (PAC)-resistance of ovarian carcinoma (OVCA) cells. We first examined the correlation between APN/CD13 expression and IC50 values of PAC in a variety of OVCA cell lines. Next we investigated whether suppression of APN/CD13 using bestatin, an inhibitor of APN/CD13 activity or the siRNA technique influenced PAC-sensitivity in ES-2 cells, which highly express APN/CD13. Moreover, we investigated the effect of bestatin on peritoneal metastasis using nude mice. We found a negative correlation between APN/CD13 expression and chemosensitivity to PAC in various carcinoma cell lines. Subsequently, we found a significant increase in PAC-sensitivity of APN/CD13 expressing OVCA cells by suppression of this enzyme, using the addition of bestatin or the siRNA technique. Furthermore, in a peritoneal metastasis model using nude mice, combination treatment with PAC and bestatin caused a synergistic increase of survival time compared with PAC alone treatment. (mean survival time: 37.7 +/- 7.0 s and 27.1 +/- 6.6 days, respectively). The present findings showed that APN/CD13 may be involved in decreased sensitivity to PAC in OVCA cells and that the mechanism of this effect involves its enzyme activity at least in part. APN/CD13 may be a therapeutic target for the treatment of OVCA in combination with chemotherapy. (c) 2007 Wiley-Liss, Inc.

Author information

Author/s: Yamashita, Mamoru (M); Kajiyama, Hiroaki (H); Terauchi, Mikio (M); Shibata, Kiyosumi (K); Ino, Kazuhiko (K); Nawa, Akihiro (A); Mizutani, Shigehiko (S); Kikkawa, Fumitaka (F);

Affiliation: Department of Obstetrics and Gynecology, Nagoya Graduate University School of Medicine, Tsurumai-Cho 65, Showa-ku, Nagoya 466-8550, Japan.

Journal and publication information

Publication Type: Journal Article

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2007-May; vol 120 (issue 10) : pp 2243-50

Dates: Created 2007/04/02; Completed 2007/06/26; Revised 2007/07/24;

PMID: 17266036, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Antigens, CD13 - antagonists & inhibitors; biosynthesis; genetics; metabolism Antineoplastic Agents, Phytogenic - pharmacology Carcinoma - drug therapy; enzymology Cell Line, Tumor Female Humans Leucine - analogs & derivatives; pharmacology

Leucine - analogs & derivatives; pharmacology Mice Mice, Inbred BALB C Mice, Nude Ovarian Neoplasms - drug therapy; enzymology Paclitaxel - pharmacology RNA, Small Interfering - genetics Xenograft Model Antitumor Assays

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Antineoplastic Agents, Phytogenic (0) ; RNA, Small Interfering (0) ; Paclitaxel (33069-62-4) ; bestatin (58970-76-6) ; Leucine (61-90-5) ; Antigens, CD13 (EC 3.4.11.2)

Related articles

These are the most related articles currently in our database:

• Chemoresistance to paclitaxel induces epithelial-mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells. 30 Jul 2007
• Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells. 25 Jul 2007
• Modulation of cisplatin sensitivity by taxol in cisplatin-sensitive and -resistant human ovarian carcinoma cell lines. 28 Feb 2000
• Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. 13 Feb 2002
• Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group Study. 27 Feb 2001
• Increased cyclooxygenase-2 (COX-2) and P-glycoprotein-170 (MDR1) expression is associated with chemotherapy resistance and poor prognosis. Analysis in ovarian carcinoma patients with low and high survival. 27 Feb 2005
• Combretastatin A4 phosphate has primary antineoplastic activity against human anaplastic thyroid carcinoma cell lines and xenograft tumors. 29 Nov 2002
• Differential impact of Raf-1 kinase activity on tumor cell resistance to paclitaxel and docetaxel. 29 Jun 2000
• Low expression of S100P associated with paclitaxel resistance in ovarian cancer cell line. 18 Aug 2008
• [Resistance of multicellular spheroids to taxol in human ovarian cancer and its mechanism] 30 Jul 2003

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a larger map of 100+ related articles.