Simvastatin protects Sertoli cells against cisplatin cytotoxicity through enhanced gap junction intercellular communication

  • Authors:
    • Lingzhi Wang
    • Jianxin Peng
    • Huansen Huang
    • Qin Wang
    • Meiling Yu
    • Liang Tao
  • View Affiliations

  • Published online on: August 10, 2015     https://doi.org/10.3892/or.2015.4192
  • Pages: 2133-2141
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Abstract

Cisplatin, an important chemotherapeutic agent against testicular germ cell cancer, induces testicular toxicity on Leydig and Sertoli cells, leading to serious side-effects such as azoospermia and infertility. In a previous study, it was found that simvastatin enhanced the sensitivity of Leydig tumor cells to chemotherapeutic toxicity through the enhancement of gap junction functions. In the present study, the effect of simvastatin on the sensitivity of normal Sertoli cells to cisplatin and the role of gap junctions in such effects was investigated. The results showed that, simvastatin attenuated cisplatin toxicity only when cells exhibited high-density culture where gap junctional formation was possible. When gap junction function was decreased by the gap junction inhibitor or by siRNA targeting connexin 43, the protective effect of simvastatin to cisplatin toxicity was substantially attenuated. Simvastatin also enhanced gap junction functions between Sertoli cells. This effect was mediated by the reduction of PKC-mediated connexin phosphorylation, thereby increasing connexin 43 membrane localization. Thus, simvastatin-induced enhancement of gap junction‑mediated intercellular communication attenuated cisplatin toxicity on Sertoli cells. This result indicated that enhancement of gap junction function by simvastatin may have bilateral beneficial effects on cisplatin‑based chemotherapy, enhancing cisplatin killing on cancer while ameliorating the reproduction toxicity.
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October-2015
Volume 34 Issue 4

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

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Spandidos Publications style
Wang L, Peng J, Huang H, Wang Q, Yu M and Tao L: Simvastatin protects Sertoli cells against cisplatin cytotoxicity through enhanced gap junction intercellular communication. Oncol Rep 34: 2133-2141, 2015
APA
Wang, L., Peng, J., Huang, H., Wang, Q., Yu, M., & Tao, L. (2015). Simvastatin protects Sertoli cells against cisplatin cytotoxicity through enhanced gap junction intercellular communication. Oncology Reports, 34, 2133-2141. https://doi.org/10.3892/or.2015.4192
MLA
Wang, L., Peng, J., Huang, H., Wang, Q., Yu, M., Tao, L."Simvastatin protects Sertoli cells against cisplatin cytotoxicity through enhanced gap junction intercellular communication". Oncology Reports 34.4 (2015): 2133-2141.
Chicago
Wang, L., Peng, J., Huang, H., Wang, Q., Yu, M., Tao, L."Simvastatin protects Sertoli cells against cisplatin cytotoxicity through enhanced gap junction intercellular communication". Oncology Reports 34, no. 4 (2015): 2133-2141. https://doi.org/10.3892/or.2015.4192