(紫杉醇卵巢癌细胞增敏）Involvement of aminopeptidase N in enhanced chemosensitivity to paclitaxel in ovarian carcinoma in vitro and in vivo.pdfVIP

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(紫杉醇卵巢癌细胞增敏）Involvement of aminopeptidase N in enhanced chemosensitivity to paclitaxel in ovarian carcinoma in vitro and in vivo.pdf

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Int. J. Cancer: 120, 2243–2250 (2007) 2007 Wiley-Liss, Inc. Involvement of aminopeptidase N in enhanced chemosensitivity to paclitaxel in ovarian carcinoma in vitro and in vivo * Mamoru Yamashita, Hiroaki Kajiyama , Mikio Terauchi, Kiyosumi Shibata, Kazuhiko Ino, Akihiro Nawa, Shigehiko Mizutani and Fumitaka Kikkawa Department of Obstetrics and Gynecology, Nagoya Graduate University School of Medicine, Showa-ku, Nagoya, Japan Aminopeptidase N (APN/CD13), a 150-kDa metalloproteinase, is a APN/CD13 was involved in protection of leukemic cells against multifunctional cell surface aminopeptidase with ubiquitous expres- apoptosis.14 In general, apoptosis is the predominant mechanism sion. Recent studies have suggested that APN/CD13 plays an impor- of cytotoxicity induced by chemotherapeutic agents. The failure tant role in tumor progression in several human malignancies. In of cancer cells to activate apoptosis may lead to multidrug resist- the current study, we investigated the role of APN/CD13 in pacli- taxel (PAC)-resistance of ovarian carcinoma (OVCA) cells. We ﬁrst ance. examined the correlation between APN/CD13 expression and IC50 In the current study, we investigated the role of APN/CD13 in values of PAC in a variety of OVCA cell lines. Next we investigated the chemosensitivity of OVCA. We ﬁrst examined the correlation whether suppression of APN/CD13 using bestatin, an inhibitor of between the expression levels of APN/CD13 and sensitivity to APN/CD13 activity or the siRNA technique inﬂuenced PAC-sensitiv- paclitaxel (PAC) in OVCA cells. Subsequently, to clarify the cel- ity in ES-2 cells, which highly express APN/CD1