Placental leucine aminopeptidase (P-LAP) expression is associated with chemosensitivity in human endometrial carcinoma
Placental leucine aminopeptidase (P-LAP) expression is associated with chemosensitivity in human endometrial carcinoma
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DOI：
10.1016/j.ygyno.2004.07.054
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发表时间：
2004-11-01
影响因子：
4.7
通讯作者：
Mizutani, S
中科院分区：
文献类型：
--
作者：
Shibata, K;Kikkawa, F;Mizutani, S
Objective.虽然晚期或复发性子宫内膜癌的治疗近年来随着紫杉醇和铂类化疗的引入而有所改善，但在大多数情况下，由于对化疗的耐药性，这种疾病仍然无法治愈。在以前的研究中，我们已经表明，胎盘亮氨酸氨基肽酶（P-AMP）与预后不良。本研究的目的是确定P-gp表达是否影响子宫内膜癌患者的化疗敏感性。在此，我们研究了在晚期和复发性子宫内膜癌中P-gp对紫杉醇和卡铂反应的影响。此外，我们还将P-cDNAcDNA转染子宫内膜癌细胞（AMEC），观察紫杉醇和卡铂对细胞生长和凋亡的影响。17例患者中15例P-CRP阳性。17例患者中有12例可评价缓解。在8例P-CRP强阳性患者中，仅2例（25%）出现PR，而4例P-CRP弱阳性患者均出现完全缓解（CR）或部分缓解（PR）。使用P-LAP过表达物（P-LAP 2和P-LAP 8）和载体对照来测定化学敏感性。与载体对照相比，P-LAP 2克隆显示出对紫杉醇和卡铂的IC 50增加1.7倍，与V1相比，P-LAP 8克隆显示出对紫杉醇和卡铂的IC 50增加1.6倍。与载体对照细胞相比，卡铂处理的细胞凋亡效应在P-LAP 2和P-LAP 8细胞中被明显抑制。在载体对照细胞中，10（-6）M卡铂在48 h时诱导的凋亡率是未处理的12.5倍。然而，在P-LAP 2和P-LAP 8克隆中，10-6 M卡铂诱导的凋亡率分别为未处理的3.2倍和5.1倍。提示P-gp参与降低子宫内膜癌化疗敏感性，可能成为子宫内膜癌的治疗靶点。(C)2004年爱思唯尔公司All rights reserved.
Objective. Although treatment for advanced or recurrent endometrial carcinoma has improved over recent years with the introduction of pactitaxel- and platinum-based chemotherapy, in most, the disease remains incurable because of resistance to chemotherapy. In the previous study, we have shown that placental leucine aminopeptidase (P-LAP) is associated with poor prognosis. The objective of this study was to determine whether P-LAP expression affects the chemosensitivity in endometrial carcinoma patients.Methods. Here, we investigated the effect of P-LAP to response for paclitaxel and carboplatin in advanced and recurrence endometrial carcinoma. Furthermore, we transfected P-LAP cDNA into endometrial carcinoma cells (AMEC) and investigated cell growth and apoptosis by paclitaxel or carboplatin.Results. In 15 of 17 patients, P-LAP was positive. Twelve of seventeen patients were evaluable for response. Among the eight patients strongly positive for P-LAP, only two patients (25%) showed PR. However, all four patients who were weakly positive for P-LAP showed either complete response (CR) or partial response (PR). P-LAP overexpressor (P-LAP2 and P-LAP8) and a vector control were used to assay chemosensitivity. P-LAP2 clone displayed a 1.7-fold increase in IC50 against paclitaxel and carboplatin when compared with the vector control, and P-LAP8 clone displayed a 1.6-fold increased in IC50 against paclitaxel and carboplatin when compared with V1. Compared to vector control cells, apoptotic effect by carboplatin treatment was clearly inhibited in P-LAP2 and P-LAP8 cells. Carboplatin, 10(-6) M, induced the 12.5-fold rate of apoptosis compared to that without treatment at 48 h in vector control cells. However, in P-LAP2 and P-LAP8 clones, 10-6 M carboplatin induced only 3.2- and 5.1-fold rates of apoptosis, respectively, compared to that of without treatment.Conclusions. P-LAP was suggested to be involved in reducing chemosensitivity and may be a therapeutic target in endometrial carcinoma. (C) 2004 Elsevier Inc. All rights reserved.