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
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
收藏
页码:292 / 299
页数:8
相关论文
共 33 条
  • [21] Connexin 43 Inhibition Sensitizes Chemoresistant Glioblastoma Cells to Temozolomide
    Murphy, Susan F.
    Varghese, Robin T.
    Lamouille, Samy
    Guo, Sujuan
    Pridham, Kevin J.
    Kanabur, Pratik
    Osimani, Alyssa M.
    Sharma, Shaan
    Jourdan, Jane
    Rodgers, Cara M.
    Simonds, Gary R.
    Gourdie, Robert G.
    Sheng, Zhi
    [J]. CANCER RESEARCH, 2016, 76 (01) : 139 - 149
  • [22] Gap junctions and tumour progression
    Naus, CCG
    [J]. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 2002, 80 (02) : 136 - 141
  • [23] Ozols RF, 2006, NEW ENGL J MED, V354, P1641
  • [24] Microtubule plus-end-tracking proteins target gap junctions directly from the cell interior to adherens junctions
    Shaw, Robin M.
    Fay, Alex J.
    Puthenveedu, Manojkumar A.
    von Zastrow, Mark
    Jan, Yuh-Nung
    Jan, Lily Y.
    [J]. CELL, 2007, 128 (03) : 547 - 560
  • [25] Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes
    Shen, Ding-Wu
    Pouliot, Lynn M.
    Hall, Matthew D.
    Gottesman, Michael M.
    [J]. PHARMACOLOGICAL REVIEWS, 2012, 64 (03) : 706 - 721
  • [26] Connexin 46 (Cx46) Gap Junctions Provide a Pathway for the Delivery of Glutathione to the Lens Nucleus
    Slavi, Nefeli
    Rubinos, Clio
    Li, Leping
    Sellitto, Caterina
    White, Thomas W.
    Mathias, Richard
    Srinivas, Miduturu
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (47) : 32694 - 32702
  • [27] Potassium channels in the Cx43 gap junction perinexus modulate ephaptic coupling: an experimental and modeling study
    Veeraraghavan, Rengasayee
    Lin, Joyce
    Keener, James P.
    Gourdie, Robert
    Poelzing, Steven
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2016, 468 (10): : 1651 - 1661
  • [28] Decitabine Rescues Cisplatin Resistance in Head and Neck Squamous Cell Carcinoma
    Viet, Chi T.
    Dang, Dongmin
    Achdjian, Stacy
    Ye, Yi
    Katz, Samuel G.
    Schmidt, Brian L.
    [J]. PLOS ONE, 2014, 9 (11):
  • [29] Cisplatin and Oxaliplatin Inhibit Gap Junctional Communication by Direct Action and by Reduction of Connexin Expression, Thereby Counteracting Cytotoxic Efficacy
    Wang, Qin
    You, Tianhui
    Yuan, Dongdong
    Han, Xu
    Hong, Xiaoting
    He, Bo
    Wang, Lingzhi
    Tong, Xuhui
    Tao, Liang
    Harris, Andrew L.
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2010, 333 (03) : 903 - 911
  • [30] Reciprocal positive regulation between Cx26 and PI3K/Akt pathway confers acquired gefitinib resistance in NSCLC cells via GJIC-independent induction of EMT
    Yang, J.
    Qin, G.
    Luo, M.
    Chen, J.
    Zhang, Q.
    Li, L.
    Pan, L.
    Qin, S.
    [J]. CELL DEATH & DISEASE, 2015, 6 : e1829 - e1829