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Article

Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication

  • Authors:
    • Lingzhi Wang
    • Yuexia Peng
    • Jianxin Peng
    • Min Shao
    • Li Ma
    • Zhuoli Zhu
    • Guocheng Zhong
    • Zhengyuan Xia
    • Huansen Huang
  • View Affiliations / Copyright

    Affiliations: Department of Anaesthesia, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China, Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Hepatobiliary Surgery, Guangdong Province Traditional Chinese Medicine Hospital, Guangzhou, Guangdong 510120, P.R. China, Department of Cardiovascular Internal Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430064, P.R. China
  • Pages: 295-304
    |
    Published online on: November 3, 2017
       https://doi.org/10.3892/ijo.2017.4188
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Abstract

Analgesics and antineoplastic drugs are often used concurrently for cancer patients. Our previous study reported that gap junctions composed of connexin32 (Cx32) was implicated in the effect of analgesics on cisplatin cytotoxicity. However, the effect of analgesic on the most widely expressed connexin (Cx), connexin43 (Cx43), and whether such effect mediates the influence on chemotherapeutic efficiency remain unknown. By manipulation of Cx43 expression or gap junction function, we found that there were gap junction-dependent and independent effect of Cx43 on temozolomide (TMZ) sensitivity in U87 glioblastoma cells. Studies on survival and apoptosis showed widely used analgesic tramadol significantly reduced TMZ-induced cytotoxicity in control and negative control cells but not shCx43-transfected cells. Proliferation assay demonstrated tramadol suppressed TMZ-induced cytotoxicity only on high density (with gap junction formation) but not on low density (without gap junction formation). Tramadol inhibited dye-coupling through gap junctions between U87 cells. Tramadol treatment for 72 h did not alter Cx43 expression, but decreased Cx43 phosphorylation accompanied with reduced p-ERK and p-JNK. Our results indicated that long-term treatment with tramadol reduced TMZ cytotoxicity in U87 cells by suppressing Cx43-composed gap junctions, suggesting identification and usage of antinociceptive drugs which do not downregulate connexin activity should have beneficial therapeutic consequences.
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Copy and paste a formatted citation
Spandidos Publications style
Wang L, Peng Y, Peng J, Shao M, Ma L, Zhu Z, Zhong G, Xia Z and Huang H: Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication. Int J Oncol 52: 295-304, 2018.
APA
Wang, L., Peng, Y., Peng, J., Shao, M., Ma, L., Zhu, Z. ... Huang, H. (2018). Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication. International Journal of Oncology, 52, 295-304. https://doi.org/10.3892/ijo.2017.4188
MLA
Wang, L., Peng, Y., Peng, J., Shao, M., Ma, L., Zhu, Z., Zhong, G., Xia, Z., Huang, H."Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication". International Journal of Oncology 52.1 (2018): 295-304.
Chicago
Wang, L., Peng, Y., Peng, J., Shao, M., Ma, L., Zhu, Z., Zhong, G., Xia, Z., Huang, H."Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication". International Journal of Oncology 52, no. 1 (2018): 295-304. https://doi.org/10.3892/ijo.2017.4188
Copy and paste a formatted citation
x
Spandidos Publications style
Wang L, Peng Y, Peng J, Shao M, Ma L, Zhu Z, Zhong G, Xia Z and Huang H: Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication. Int J Oncol 52: 295-304, 2018.
APA
Wang, L., Peng, Y., Peng, J., Shao, M., Ma, L., Zhu, Z. ... Huang, H. (2018). Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication. International Journal of Oncology, 52, 295-304. https://doi.org/10.3892/ijo.2017.4188
MLA
Wang, L., Peng, Y., Peng, J., Shao, M., Ma, L., Zhu, Z., Zhong, G., Xia, Z., Huang, H."Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication". International Journal of Oncology 52.1 (2018): 295-304.
Chicago
Wang, L., Peng, Y., Peng, J., Shao, M., Ma, L., Zhu, Z., Zhong, G., Xia, Z., Huang, H."Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43‑mediated gap junction intercellular communication". International Journal of Oncology 52, no. 1 (2018): 295-304. https://doi.org/10.3892/ijo.2017.4188
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