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学科主题临床医学
TKTL1 modulates the response of paclitaxel-resistant human ovarian cancer cells to paclitaxel
Zheng, Xing; Li, Hongxia
通讯作者Li, Hongxia(1)
关键词Ovarian cancer Paclitaxel resistance TKTL1 RNA interference Redox
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
2018-09-05
DOI10.1016/j.bbrc.2018.06.011
503期:2页:572-579
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]TRANSKETOLASE TKTL1 ; AEROBIC GLYCOLYSIS ; DRUG-RESISTANCE ; TUMOR-CELLS ; IN-VITRO ; EXPRESSION ; PROLIFERATION ; CARCINOMA ; LINE ; CHEMOTHERAPY
英文摘要

Transketolase-like 1 (TKTL1) plays an important role in the pentose phosphate pathway (PPP) branch. The main obstacle of ovarian cancer treatment is chemotherapeutic resistance. We investigated whether inhibiting TKTL1 in OC3/TAX300 cells could re-sensitize paclitaxel-resistant cells to paclitaxel and proposed a mechanism of action. Western blotting revealed that TKTL1 expression levels in OC3/Tax300 cells were significantly higher than those in OC3 cells. Inhibition of TKTL1 significantly decreased the cellular proliferation rate and IC50 for paclitaxel. Metabolomics revealed that NADPH levels were reduced in the si-TKTL1 group, whereas NADP(+) was increased compared with the level in the negative si-TKTL1 group. A 2.2-fold increase in the ROS level and an obvious increase in the cell apoptosis rate were observed in the si-TICTL1+paclitaxel group compared with those in the negative si-TKTL1+paclitaxel and OC3/Tax300 + paclitaxel groups. Western blotting revealed that Bax and Caspase 3 proteins were up regulated, whereas Bcl-2 expression was down-regulated. Quantitative RT-PCR revealed no changes in gst-pi or mrp1 gene expression in the three groups, whereas GSH levels were reduced in the si-TKTL1 group as verified by metabolomics. TKTL1 inhibition also reduced tumor growth in vivo. Collectively, TKTL1 down-regulation sensitized paclitaxel-resistant OC3/Tax300 ovarian cancer cells to paclitaxel. (C) 2018 Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000442711200026
通讯作者邮箱lihx_sjt@163.com
第一作者单位Peking Univ, Dept Obstet & Gynecol, Sch Clin Med 9, 10 Tieyi Rd, Beijing, Peoples R China
通讯作者单位Peking Univ, Dept Obstet & Gynecol, Sch Clin Med 9, 10 Tieyi Rd, Beijing, Peoples R China
ISSN0006-291X
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/143079
专题北京大学第九临床医学院
作者单位Peking Univ, Dept Obstet & Gynecol, Sch Clin Med 9, 10 Tieyi Rd, Beijing, Peoples R China
推荐引用方式
GB/T 7714
Zheng, Xing,Li, Hongxia. TKTL1 modulates the response of paclitaxel-resistant human ovarian cancer cells to paclitaxel[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2018,503(2):572-579.
APA Zheng, Xing,&Li, Hongxia.(2018).TKTL1 modulates the response of paclitaxel-resistant human ovarian cancer cells to paclitaxel.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,503(2),572-579.
MLA Zheng, Xing,et al."TKTL1 modulates the response of paclitaxel-resistant human ovarian cancer cells to paclitaxel".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 503.2(2018):572-579.
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