Gefitinib enhances oxaliplatin-induced apoptosis mediated by Src and PKC-modulated gap junction function

  • Authors:
    • Jian-Feng Wu
    • Jie Ji
    • Shu-Ying Dong
    • Bei-Bei Li
    • Mei-Ling Yu
    • Dan-Dan Wu
    • Liang Tao
    • Xu-Hui Tong
  • View Affiliations

  • Published online on: October 11, 2016     https://doi.org/10.3892/or.2016.5156
  • Pages: 3251-3258
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Abstract

Chemotherapeutic drug-induced apoptosis is enhanced by gap junction intercellular communication (GJIC) in a variety of tumor cells. Oxaliplatin and gefitinib are the most widely used chemotherapeutic drugs. However, the synergistic influence remains unknown in testicular cancer chemotherapy. The aim of the present study was to investigate the apoptosis induced by oxaliplatin combined with gefitinib and the potential mechanisms in I-10 testicular cancer cells. The results showed that gefitinib significantly enhanced oxaliplatin-induced apoptosis. Furthermore, the ratio of Bcl-2/Bax and the cleavage of caspase-3 and -9 were increased by gefitinib during oxaliplatin-induced apoptosis. The oxaliplatin-induced apoptosis was enhanced through the upregulation of gap junction (GJ) channels composed of connexin 43 (Cx43) by gefitinib. The mechanism of GJIC enhancement involved the suppression by gefitinib of the expression levels of Src and PKC, which phosphorylate Cx43 and reduce GJIC. PP2 (Src inhibitor) and GF109203X (PKC inhibitor) also enhanced GJIC function. Our findings demonstrated that gefitinib enhanced oxaliplatin-induced apoptosis in I-10 cells and gefitinib upregulated the GJIC by inhibiting Src and PKC-modulated Cx43 phosphorylation.
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December-2016
Volume 36 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wu J, Ji J, Dong S, Li B, Yu M, Wu D, Tao L and Tong X: Gefitinib enhances oxaliplatin-induced apoptosis mediated by Src and PKC-modulated gap junction function. Oncol Rep 36: 3251-3258, 2016.
APA
Wu, J., Ji, J., Dong, S., Li, B., Yu, M., Wu, D. ... Tong, X. (2016). Gefitinib enhances oxaliplatin-induced apoptosis mediated by Src and PKC-modulated gap junction function. Oncology Reports, 36, 3251-3258. https://doi.org/10.3892/or.2016.5156
MLA
Wu, J., Ji, J., Dong, S., Li, B., Yu, M., Wu, D., Tao, L., Tong, X."Gefitinib enhances oxaliplatin-induced apoptosis mediated by Src and PKC-modulated gap junction function". Oncology Reports 36.6 (2016): 3251-3258.
Chicago
Wu, J., Ji, J., Dong, S., Li, B., Yu, M., Wu, D., Tao, L., Tong, X."Gefitinib enhances oxaliplatin-induced apoptosis mediated by Src and PKC-modulated gap junction function". Oncology Reports 36, no. 6 (2016): 3251-3258. https://doi.org/10.3892/or.2016.5156