Ad-PUMA sensitizes drug-resistant choriocarcinoma cells to chemotherapeutic agents

被引：38

作者：

Chen, Yan ^{[1
,2
,3
]}

Qian, Haili ^{[1
]}

Wang, Haijuan ^{[1
]}

Zhang, Xueyan ^{[1
]}

Fu, Ming ^{[1
]}

Liang, Xiao ^{[1
]}

Ma, Yan ^{[2
]}

Zhan, Qimin ^{[1
]}

Lin, Chen ^{[1
]}

Xiang, Yang ^{[2
]}

机构：

[1] Chinese Acad Med Sci, Peking Union Med Coll, Inst Canc, State Key Lab Mol Oncol, Beijing 100021, Peoples R China

[2] Chinese Acad Med Sci, Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, Beijing 100730, Peoples R China

[3] N China Coal Med Coll Attached Hosp, Hebei, Peoples R China

来源：

GYNECOLOGIC ONCOLOGY | 2007年 / 107卷 / 03期

基金：

中国国家自然科学基金;

关键词：

PUMA; choriocarcinoma; drug resistance; chemosensitivity; gone therapy;

D O I：

10.1016/j.ygyno.2007.08.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose/Objective. To investigate whether exogenous PUMA expression suppresses the growth of drug-resistant choriocarcinoma cells and sensitizes them to chemotherapeutic agents. Methods. An adenovirus expressing PUMA (Ad-PUMA), alone or in combination with chemotherapeutic agents(5-FU, vp 16, MTX), was used to treat drug-resistant choriocarcinoma cells jeg-3/vp 16 and parental jeg-3. The growth inhibitory and proapoptotic effects of Ad-PUMA both in vitro and in vivo were examined. The mechanisms of PUMA-mediated growth suppression and apoptosis were investigated by an analysis of caspase 3 activation and the change of mitochondrial membrane potential. The levels of PUMA, p53 and caspase 3 were detected by Western blotting. Result. PUMA was expressed lower in jeg-3/vp 16 than in jeg-3. jeg-3/vp 16 responded much less sensitively to 5-FU and vp 16 treatment than jeg-3, though PUMA was up-regulated in both cells. Exogenous PUMA expression resulted in potent growth suppression of jeg-3/vp 16 and jeg-3 through induction of apoptosis. Ad-PUMA sensitized jeg-3 and jeg-3/vp 16 to chemotherapeutic agents. When Ad-PUMA 10MOI and 5-FU, vp 16 or MTX were combined respectively, IC50 of drugs decreased by 8.66-, 18.66- and 13.06-fold compared with those treated by anticancer drugs alone in jeg-3/vp 16, while in jeg-3, IC50 decreased only by 1.80-, 1.78- and 2.76-fold. Ad-PUMA restored the sensitivity of choriocarcinoma cells to chemotherapeutic agents by enhancing apoptosis induced by anticancer drugs. Similar results could be observed in vivo. Xenograft tumors were inhibited by Ad-PUMA or vp 16. In the drug-resistant group, the inhibitory rate increased from 14.57% to 78.93% in vp 16 and vp 16 combined with Ad-PUMA subgroups. While in the parental group, the inhibitory rate increased but slightly, from 66.39% to 71.56%. Conclusion. PUMA is an important player in the therapeutic responses to chemotherapeutic agents of choriocarcinoma cells. In addition to its role in inhibiting tumor growth, low dose of Ad-PUMA significantly restored the sensitivity of choriocarcinoma cells to chemotherapeutic agents in vitro and in vivo. Exogenous PUMA is potentially useful as a sensitizer in treating drug-resistant choriocarcinoma. (C) 2007 Elsevier Inc. All rights reserved.

引用

页码：505 / 512

页数：8

共 27 条

[21] Overexpression of caspase-3s splice variant in locally advanced breast carcinoma is associated with poor response to neoadjuvant chemotherapy [J].