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Article

Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes

  • Authors:
    • Nan Tang
    • Jinghua Liu
    • Bo Chen
    • Yuan Zhang
    • Meiling Yu
    • Ziqing Cai
    • Hongpeng Chen
  • View Affiliations / Copyright

    Affiliations: School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China, School of Information Engineering, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China
  • Pages: 2689-2694
    |
    Published online on: March 7, 2017
       https://doi.org/10.3892/mmr.2017.6295
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Abstract

The effect of gap junction intercellular communication (GJIC) on docetaxel-induced hepatotoxicity and its underlying mechanisms are largely unknown. The present study involved investigating the effect of downregulating GJs derived from connexin (Cx) 32 in BRL-3A cells by three different mechanisms: Using a low-density culture; suppression of Cx32 using small interfering RNA; and use of the chemical inhibitor 2‑aminoethoxydiphenyl borate (2‑APB), all of which led to attenuated docetaxel hepatotoxicity. In order to investigate the relevant mechanisms involved, apoptosis and caspase activities of BRL‑3A cells were determined. The increase of apoptosis and the activation of caspase‑3 and caspase‑9, but not caspase-8, were detected following cell exposure with docetaxel, demonstrating that the mitochondrial‑mediated apoptosis pathway is largely responsible for docetaxel hepatotoxicity. However, reduced apoptosis and caspase‑3, and ‑9 activities were observed following docetaxel application when BRL‑3A GJIC was deficient from the knockdown of Cx32 expression or pretreatment with 2‑APB. These observations illustrate that GJs are important in docetaxel-induced hepatotoxicity. Furthermore, inhibition of GJIC could prevent amplification of toxicity to docetaxel. Due to GJIC blockage, this hepatoprotection was associated, in part, with decreasing apoptosis of BRL‑3A cells through the mitochondrial pathway. The present study provides evidence for potential therapeutic targets for the treatment of docetaxel-induced liver injury.
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Copy and paste a formatted citation
Spandidos Publications style
Tang N, Liu J, Chen B, Zhang Y, Yu M, Cai Z and Chen H: Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes. Mol Med Rep 15: 2689-2694, 2017.
APA
Tang, N., Liu, J., Chen, B., Zhang, Y., Yu, M., Cai, Z., & Chen, H. (2017). Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes. Molecular Medicine Reports, 15, 2689-2694. https://doi.org/10.3892/mmr.2017.6295
MLA
Tang, N., Liu, J., Chen, B., Zhang, Y., Yu, M., Cai, Z., Chen, H."Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes". Molecular Medicine Reports 15.5 (2017): 2689-2694.
Chicago
Tang, N., Liu, J., Chen, B., Zhang, Y., Yu, M., Cai, Z., Chen, H."Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes". Molecular Medicine Reports 15, no. 5 (2017): 2689-2694. https://doi.org/10.3892/mmr.2017.6295
Copy and paste a formatted citation
x
Spandidos Publications style
Tang N, Liu J, Chen B, Zhang Y, Yu M, Cai Z and Chen H: Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes. Mol Med Rep 15: 2689-2694, 2017.
APA
Tang, N., Liu, J., Chen, B., Zhang, Y., Yu, M., Cai, Z., & Chen, H. (2017). Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes. Molecular Medicine Reports, 15, 2689-2694. https://doi.org/10.3892/mmr.2017.6295
MLA
Tang, N., Liu, J., Chen, B., Zhang, Y., Yu, M., Cai, Z., Chen, H."Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes". Molecular Medicine Reports 15.5 (2017): 2689-2694.
Chicago
Tang, N., Liu, J., Chen, B., Zhang, Y., Yu, M., Cai, Z., Chen, H."Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes". Molecular Medicine Reports 15, no. 5 (2017): 2689-2694. https://doi.org/10.3892/mmr.2017.6295
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