The expression of dipeptidyl peptidase IV (DPPIV/CD26) is associated with enhanced chemosensitivity to paclitaxel in epithelial ovarian carcinoma cells
The expression of dipeptidyl peptidase IV (DPPIV/CD26) is associated with enhanced chemosensitivity to paclitaxel in epithelial ovarian carcinoma cells
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DOI：
10.1111/j.1349-7006.2009.01378.x
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发表时间：
2010-02-01
期刊：
影响因子：
5.7
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
--
作者：
Kajiyama, Hiroaki;Shibata, Kiyosumi;Kikkawa, Fumitaka
二肽基肽酶IV（DPPIV/CD 26）是一种多功能的细胞表面氨肽酶，广泛表达于不同的细胞类型。最近的研究表明，DPPIV在几种人类恶性肿瘤的肿瘤进展中起重要作用。在目前的研究中，我们研究了DPPIV在上皮性卵巢癌（EOC）细胞紫杉醇耐药中的作用。我们首先研究了不同EOC细胞系中DPPIV表达水平与紫杉醇敏感性之间的相关性。随后，为了阐明DPPIV的细胞功能，我们使用稳定转染DPPIV的EOC细胞在体外和体内研究了该分子在EOC对紫杉醇敏感性中的作用。我们发现在不同的EOC细胞系中DPPIV表达和紫杉醇敏感性之间存在正相关。此外，我们观察到DPPIV过表达的EOC细胞对紫杉醇的敏感性显著增加。此外，在紫杉醇敏感性没有明显的改变，注意到在DPPIV转染或天然DPPIV过表达的EOC细胞中加入DPPIV活性的特异性抑制剂。在用紫杉醇处理的皮下鼠模型中，在第39天，DPPIV转染的细胞接种组的肿瘤大小与载体转染的细胞接种组一样大。相比之下，在第61天，前者小于后者。目前的研究结果表明，DPPIV可能参与了EOC细胞对紫杉醇敏感性的增加，而不管DPPIV活性的参与。（Cancer Sci 2010; 101：347-354）
Dipeptidyl peptidase IV (DPPIV/CD26) is a multifunctional cell surface aminopeptidase that is widely expressed in different cell types. Recent studies have suggested that DPPIV plays an important role in tumor progression in several human malignancies. In the current study, we investigated the role of DPPIV in paclitaxel resistance in epithelial ovarian carcinoma (EOC) cells. We first examined the correlation between expression levels of DPPIV and sensitivity to paclitaxel in various EOC cell lines. Subsequently, to clarify the cellular functions of DPPIV, we investigated the role of this molecule in the sensitivity of EOC to paclitaxel in vitro and in vivo using stably DPPIV-transfected EOC cells. We identified a positive correlation between DPPIV expression and paclitaxel sensitivity in various EOC cell lines. In addition, we observed a significant increase in the paclitaxel sensitivity of DPPIV-overexpressing EOC cells. Furthermore, no apparent alteration in paclitaxel sensitivity was noted by the addition of a specific inhibitor of DPPIV activity in DPPIV-transfected or natively DPPIV-overexpressing EOC cells. In a subcutaneous murine model treated with paclitaxel, on Day 39, the tumor size of the DPPIV-transfected cell-inoculated group was as large as that of the vector-transfected cell-inoculated group. In contrast, on Day 61, the former was smaller than the latter. The present findings show that DPPIV may be involved in the increased sensitivity to paclitaxel of EOC cells regardless of the involvement of DPPIV activity. (Cancer Sci 2010; 101: 347-354)