The cytoplasmic translocation of Cx32 mediates cisplatin resistance in ovarian cancer cells

被引：17

作者：

Wu, Weili ^{[1
]}

Fan, Lixia ^{[1
]}

Bao, Zeqing ^{[2
]}

Zhang, Yu ^{[1
]}

Peng, Yuexia ^{[1
]}

Shao, Min ^{[1
]}

Xiang, Yuke ^{[1
]}

Zhang, Xiaomin ^{[1
]}

Wang, Qin ^{[1
]}

Tao, Liang ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Pharmacol, 74 Zhongshan 2nd Rd, Guangzhou 510080, Guangdong, Peoples R China

[2] Zhaoqing Med Coll, Pharmacol Teaching & Res Sect, Zhaoqing 526020, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2017年 / 487卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Cisplatin; Resistance; Ovarian cancer; Cx32; Gap junction; GAP JUNCTIONAL COMMUNICATION; IN-VITRO; PROGRESSION; EXPRESSION; PATHWAY; TEMOZOLOMIDE; CONNEXINS; CHANNEL; GENE; EMT;

D O I：

10.1016/j.bbrc.2017.04.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ovarian cancer is the most lethal gynecologic malignancy, and cisplatin is one of the first-line chemotherapeutic agents. However, acquired cisplatin resistance prevents the successful treatment of patients with ovarian cancer. Gap junction(GJ) and connexin (Cx) are closely related to tumor formation, but the relationship between cisplatin resistance and GJ or Cx are undetermined. In this study, we established the cisplatin-resistant human ovarian cancer cell line A2780-CDDP. Here we showed that cisplatin resistance was correlated to the loss of GJ and the upregulation of Cx32 expression. Enhancing GJ in A2780-CDDP cells could increase the apoptotic response to cisplatin treatment. Furthermore, although Cx32 expression was increased in A2780-CDDP cells, it was more localized to the cytoplasm rather than in the membrane, and knockdown of Cx32 in A2780-CDDP cells sensitized them to cisplatin treatment. In summary, Cx32 is involved in cisplatin resistance, and cytoplasmic Cx32 plays an important role in chemoresistance. (C) 2017 Elsevier Inc. All rights reserved.

引用

页码：292 / 299

页数：8

共 33 条

[1] The relationship between connexins, gap junctions, tissue architecture and tumour invasion, as studied in a novel in vitro model of HPV-16-associated cervical cancer progression [J].

Aasen, T ;

Hodgins, MB ;

Edward, M ;

Graham, SV .

ONCOGENE, 2003, 22 (39) :7969-7980

[2] Intraperitoneal cisplatin and paclitaxel in ovarian cancer [J].

Armstrong, DK ;

Bundy, B ;

Wenzel, L ;

Huang, HQ ;

Baergen, R ;

Lele, S ;

Copeland, LJ ;

Walker, JL ;

Burger, RA .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (01) :34-43

[3] Cisplatin and the sensitive cell [J].

Bagby, GC ;

Olson, SB .

NATURE MEDICINE, 2003, 9 (05) :513-514

[4] Replication fork stability confers chemoresistance in BRCA-deficient cells [J].

Chaudhuri, Arnab Ray ;

Callen, Elsa ;

Ding, Xia ;

Gogola, Ewa ;

Duarte, Alexandra A. ;

Lee, Ji-Eun ;

Wong, Nancy ;

Lafarga, Vanessa ;

Calvo, Jennifer A. ;

Panzarino, Nicholas J. ;

John, Sam ;

Day, Amanda ;

Crespo, Anna Vidal ;

Shen, Binghui ;

Starnes, Linda M. ;

de Ruiter, Julian R. ;

Daniel, Jeremy A. ;

Konstantinopoulos, Panagiotis A. ;

Cortez, David ;

Cantor, Sharon B. ;

Fernandez-Capetillo, Oscar ;

Ge, Kai ;

Jonkers, Jos ;

Rottenberg, Sven ;

Sharan, Shyam K. ;

Nussenzweig, Andre .

NATURE, 2016, 535 (7612) :382-+

[5] MicroRNA-451 sensitizes lung cancer cells to cisplatin through regulation of Mcl-1 [J].

Cheng, Dezhi ;

Xu, Yi ;

Sun, Changzheng ;

He, Zhifeng .

MOLECULAR AND CELLULAR BIOCHEMISTRY, 2016, 423 (1-2) :85-91

[6] The role of connexins in prostate cancer promotion and progression [J].

Czyz, Jaroslaw ;

Szpak, Katarzyna ;

Madeja, Zbigniew .

NATURE REVIEWS UROLOGY, 2012, 9 (05) :274-282

[7] Cardiac Cx43, Cx40 and Cx45 co-assembling: involvement of connexins epitopes in formation of hemichannels and Gap junction channels [J].

Desplantez, Thomas .

BMC CELL BIOLOGY, 2017, 18

[8] Propagation Distance of the α-Particle-Induced Bystander Effect: The Role of Nuclear Traversal and Gap Junction Communication [J].

Gaillard, Sylvain ;

Pusset, David ;

de Toledo, Sonia M. ;

Fromm, Michel ;

Azzam, Edouard I. .

RADIATION RESEARCH, 2009, 171 (05) :513-520

[9] Gap junctions in the ovary: Expression, localization and function [J].

Gershon, Eran ;

Plaks, Vicki ;

Dekel, Nava .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2008, 282 (1-2) :18-25

[10] Connexin43 confers Temozolomide resistance in human glioma cells by modulating the mitochondrial apoptosis pathway [J].

Gielen, Paul R. ;

Aftab, Qurratulain ;

Ma, Noreen ;

Chen, Vincent C. ;

Hong, Xiaoting ;

Lozinsky, Shannon ;

Naus, Christian C. ;

Sin, Wun Chey .

NEUROPHARMACOLOGY, 2013, 75 :539-548

← 1 2 3 4 →