Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
September-2017 Volume 14 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2017 Volume 14 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Deficiency of gap junction composed of connexin43 contributes to oxaliplatin resistance in colon cancer cells

  • Authors:
    • Min Su
    • Qi Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Hospital Affiliated to Hubei University of Arts and Science/Xiangyang Central Hospital, Xiangyang, Hubei 441021, P.R. China
  • Pages: 3669-3674
    |
    Published online on: July 18, 2017
       https://doi.org/10.3892/ol.2017.6598
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Although comprehensive strategies in the treatment of colorectal cancer have been developed for a number of years, the five‑year survival rate of metastatic colon cancer remains less than 10%. Oxaliplatin, a commonly used chemotherapeutic agent for metastatic colon cancer, improves the response rate of patients and prolongs patients' progression‑free survival. However, the generation of resistance limits the clinical application of oxaliplatin, and the mechanisms of this remain unclear. The present study mainly investigated the effect of the gap junction (GJ) composed of connexin43 (Cx43) on oxaliplatin cytotoxicity in colon cancer cells. Three different methods with distinct mechanisms were used to change the function of Cx43 GJs, including cell culture at different densities, pretreatment with a specific inhibitor or enhancer, and special gene knockdown, to observe the cytotoxicity of oxaliplatin and the level of reactive oxygen species (ROS) mediated by Cx43 GJs. The results revealed that the cytotoxicity of oxaliplatin and the level of ROS were decreased with the downregulation of Cx43 GJ function, but exacerbated with the upregulation of Cx43 GJ function. Moreover, ROS scavenging with N‑acetyl‑L‑cysteine and apocynin decreased the cytotoxicity of oxaliplatin. We concluded that the loss of GJ composed of Cx43 contributed to the resistance of oxaliplatin in colon cancer cells, and the mechanism was associated with intracellular ROS alternation.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Hirschi B, Gallmeier E, Ziesch A, Marschall M and Kolligs FT: Genetic targeting of B-RafV600E affects survival and proliferation and identifies selective agents against BRAF-mutant colorectal cancer cells. Mol Cancer. 13:1222014. View Article : Google Scholar : PubMed/NCBI

2 

Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global patterns and trends in colorectal cancer incidence and mortality. Gut. 66:686–691. 2017. View Article : Google Scholar

3 

Tan S, Peng X, Peng W, Zhao Y and Wei Y: Enhancement of oxaliplatin-induced cell apoptosis and tumor suppression by 3-methyladenine in colon cancer. Oncol Lett. 9:2056–2062. 2015.PubMed/NCBI

4 

Fan F, Gray MJ, Dallas NA, Yang AD, Van Buren G II, Camp ER and Ellis LM: Effect of chemotherapeutic stress on induction of vascular endothelial growth factor family members and receptors in human colorectal cancer cells. Mol Cancer Ther. 7:3064–3070. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Luo C, Yuan D, Li X, Yao W, Luo G, Chi X, Li H, Irwin MG, Xia Z and Hei Z: Propofol attenuated acute kidney injury after orthotopic liver transplantation via inhibiting gap junction composed of connexin 32. Anesthesiology. 122:72–86. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Chen X, Kong X, Zhuang W, Teng B, Yu X, Hua S, Wang S, Liang F, Ma D, Zhang S, et al: Dynamic changes in protein interaction between AKAP95 and Cx43 during cell cycle progression of A549 cells. Sci Rep. 6:212242016. View Article : Google Scholar : PubMed/NCBI

7 

Sirnes S, Bruun J, Kolberg M, Kjenseth A, Lind GE, Svindland A, Brech A, Nesbakken A, Lothe RA, Leithe E and Rivedal E: Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease outcome. Int J Cancer. 131:570–581. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Gielen PR, Aftab Q, Ma N, Chen VC, Hong X, Lozinsky S, Naus CC and Sin WC: Connexin43 confers Temozolomide resistance in human glioma cells by modulating the mitochondrial apoptosis pathway. Neuropharmacology. 75:539–548. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Yu M, Zhang C, Li L, Dong S, Zhang N and Tong X: Cx43 reverses the resistance of A549 lung adenocarcinoma cells to cisplatin by inhibiting EMT. Oncol Rep. 31:2751–2758. 2014.PubMed/NCBI

10 

Lin S, Lei K, Du W, Yang L, Shi H, Gao Y, Yin P, Liang X and Liu J: Enhancement of oxaliplatin sensitivity in human colorectal cancer by hypericin mediated photodynamic therapy via ROS-related mechanism. Int J Biochem Cell Biol. 71:24–34. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Wang Q, You T, Yuan D, Han X, Hong X, He B, Wang L, Tong X, Tao L and Harris AL: Cisplatin and oxaliplatin inhibit gap junctional communication by direct action and by reduction of connexin expression, thereby counteracting cytotoxic efficacy. J Pharmacol Exp Ther. 333:903–911. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Yuan D, Wang Q, Wu D, Yu M, Zhang S, Li L, Tao L and Harris AL: Monocyte-endothelial adhesion is modulated by Cx43-stimulated ATP release from monocytes. Biochem Biophys Res Commun. 420:536–541. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Luo C, Yuan D, Zhao W, Chen H, Luo G, Su G and Hei Z: Sevoflurane ameliorates intestinal ischemia-reperfusion-induced lung injury by inhibiting the synergistic action between mast cell activation and oxidative stress. Mol Med Rep. 12:1082–1090. 2015.PubMed/NCBI

14 

Lee W, Belkhiri A, Lockhart AC, Merchant N, Glaeser H, Harris EI, Washington MK, Brunt EM, Zaika A, Kim RB and El-Rifai W: Overexpression of OATP1B3 confers apoptotic resistance in colon cancer. Cancer Res. 68:10315–10323. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Leone F, Artale S, Marino D, Cagnazzo C, Cascinu S, Pinto C, Fornarini G, Tampellini M, Di Fabio F, Sartore-Bianchi A, et al: Panitumumab in combination with infusional oxaliplatin and oral capecitabine for conversion therapy in patients with colon cancer and advanced liver metastases. The MetaPan study. Cancer. 119:3429–3435. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Taieb J, Zaanan A, Le Malicot K, Julié C, Blons H, Mineur L, Bennouna J, Tabernero J, Mini E, Folprecht G, et al: Prognostic effect of BRAF and KRAS mutations in patients with stage III colon cancer treated with leucovorin, fluorouracil, and oxaliplatin with or without cetuximab: A post hoc analysis of the PETACC-8 trial. JAMA Oncol. 1–11. 2016.PubMed/NCBI

17 

Anderson BJ and Peterson LL: Systemic capillary leak syndrome in a patient receiving adjuvant oxaliplatin for locally advanced colon cancer. J Oncol Pharm Pract. 22:725–728. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Segretain D, Decrouy X, Dompierre J, Escalier D, Rahman N, Fiorini C, Mograbi B, Siffroi JP, Huhtaniemi I, Fenichel P and Pointis G: Sequestration of connexin43 in the early endosomes: An early event of Leydig cell tumor progression. Mol Carcinog. 38:179–187. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Leithe E, Sirnes S, Omori Y and Rivedal E: Downregulation of gap junctions in cancer cells. Crit Rev Oncog. 12:225–256. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Mesnil M, Crespin S, Avanzo JL and Zaidan-Dagli ML: Defective gap junctional intercellular communication in the carcinogenic process. Biochim Biophys Acta. 1719:125–145. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Kardami E, Dang X, Iacobas DA, Nickel BE, Jeyaraman M, Srisakuldee W, Makazan J, Tanguy S and Spray DC: The role of connexins in controlling cell growth and gene expression. Prog Biophys Mol Biol. 94:245–264. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Shao Q, Wang H, McLachlan E, Veitch GI and Laird DW: Down-regulation of Cx43 by retroviral delivery of small interfering RNA promotes an aggressive breast cancer cell phenotype. Cancer Res. 65:2705–2711. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Avanzo JL, Mesnil M, Hernandez-Blazquez FJ, Mackowiak II, Mori CM, da Silva TC, Oloris SC, Gárate AP, Massironi SM, Yamasaki H and Dagli ML: Increased susceptibility to urethane-induced lung tumors in mice with decreased expression of connexin43. Carcinogenesis. 25:1973–1982. 2004. View Article : Google Scholar : PubMed/NCBI

24 

He B, Tong X, Wang L, Wang Q, Ye H, Liu B, Hong X, Tao L and Harris AL: Tramadol and flurbiprofen depress the cytotoxicity of cisplatin via their effects on gap junctions. Clin Cancer Res. 15:5803–5810. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Hong X, Wang Q, Yang Y, Zheng S, Tong X, Zhang S, Tao L and Harris AL: Gap junctions propagate opposite effects in normal and tumor testicular cells in response to cisplatin. Cancer Lett. 317:165–171. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Zhao Y, Liu B, Wang Q, Yuan D, Yang Y, Hong X, Wang X and Tao L: Propofol depresses the cytotoxicity of X-ray irradiation through inhibition of gap junctions. Anesth Analg. 112:1088–1095. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Sanson M, Marcaud V, Robin E, Valéry C, Sturtz F and Zalc B: Connexin 43-mediated bystander effect in two rat glioma cell models. Cancer Gene Ther. 9:149–155. 2002. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Su M and Zhang Q: Deficiency of gap junction composed of connexin43 contributes to oxaliplatin resistance in colon cancer cells. Oncol Lett 14: 3669-3674, 2017.
APA
Su, M., & Zhang, Q. (2017). Deficiency of gap junction composed of connexin43 contributes to oxaliplatin resistance in colon cancer cells. Oncology Letters, 14, 3669-3674. https://doi.org/10.3892/ol.2017.6598
MLA
Su, M., Zhang, Q."Deficiency of gap junction composed of connexin43 contributes to oxaliplatin resistance in colon cancer cells". Oncology Letters 14.3 (2017): 3669-3674.
Chicago
Su, M., Zhang, Q."Deficiency of gap junction composed of connexin43 contributes to oxaliplatin resistance in colon cancer cells". Oncology Letters 14, no. 3 (2017): 3669-3674. https://doi.org/10.3892/ol.2017.6598
Copy and paste a formatted citation
x
Spandidos Publications style
Su M and Zhang Q: Deficiency of gap junction composed of connexin43 contributes to oxaliplatin resistance in colon cancer cells. Oncol Lett 14: 3669-3674, 2017.
APA
Su, M., & Zhang, Q. (2017). Deficiency of gap junction composed of connexin43 contributes to oxaliplatin resistance in colon cancer cells. Oncology Letters, 14, 3669-3674. https://doi.org/10.3892/ol.2017.6598
MLA
Su, M., Zhang, Q."Deficiency of gap junction composed of connexin43 contributes to oxaliplatin resistance in colon cancer cells". Oncology Letters 14.3 (2017): 3669-3674.
Chicago
Su, M., Zhang, Q."Deficiency of gap junction composed of connexin43 contributes to oxaliplatin resistance in colon cancer cells". Oncology Letters 14, no. 3 (2017): 3669-3674. https://doi.org/10.3892/ol.2017.6598
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team