Open Access

Tetramethylpyrazine-mediated regulation of CXCR4 in retinoblastoma is sensitive to cell density

  • Authors:
    • Nandan Wu
    • Lijun Xu
    • Ying Yang
    • Na Yu
    • Zhang Zhang
    • Pei Chen
    • Jing Zhang
    • Mingjun Tang
    • Meng Yuan
    • Jian Ge
    • Keming Yu
    • Jing Zhuang
  • View Affiliations

  • Published online on: March 7, 2017     https://doi.org/10.3892/mmr.2017.6293
  • Pages: 2481-2488
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Retinoblastoma is the most common ocular tumor in children, and it causes extensive damage. Current treatment options for retinoblastoma include surgery, chemotherapy, radiotherapy and cryotherapy. However, the majority of chemotherapy medicines cause complications and side effects that lead to severe impairment of patient health. Previous studies have reported that tetramethylpyrazine (TMP), which is an extract of the Chinese herbal medicine Chuanxiong, reduces the risk of multidrug resistance in chemotherapy and inhibits the proliferation and metastasis of various types of cancer cells. However, the underlying molecular mechanism of TMP in retinoblastoma remains unclear. The current study demonstrated that C-X-C chemokine receptor type 4 (CXCR4) was expressed in WERI‑Rb1 cells and in retinoblastoma. Using reverse transcription‑quantitative polymerase chain reaction and western blotting techniques, the current study demonstrated that TMP significantly downregulated the expression of CXCR4 in WERI‑Rb1 cells cultured at high density, whereas it had a minor effect in low‑density WERI‑Rb1 cells; additionally, this effect occurred in a time‑dependent manner. TMP inhibited the proliferation of WERI‑Rb1 cells as effectively as a CXCR4 antagonist, AMD3100, consistent with a role of CXCR4 in cancer development. Notably, TMP did not affect the cell cycle of cells cultured at low density (1x105 cells/ml), whereas it induced G1‑phase arrest in high‑density cells (7.5x105 cells/ml; P<0.05). In addition, the expression of CXCR4 in primary rat retinal neurocytes was significantly downregulated by TMP treatment, and this treatment protected primary rat retinal neurocytes from H2O2‑induced damage. Thus, the results of this study indicate that TMP is a potential candidate for use in treatment of retinoblastoma, and also provides novel insights into the mechanisms of the anti‑cancer and neuroprotective effects of this extract.
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May-2017
Volume 15 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wu N, Xu L, Yang Y, Yu N, Zhang Z, Chen P, Zhang J, Tang M, Yuan M, Ge J, Ge J, et al: Tetramethylpyrazine-mediated regulation of CXCR4 in retinoblastoma is sensitive to cell density. Mol Med Rep 15: 2481-2488, 2017
APA
Wu, N., Xu, L., Yang, Y., Yu, N., Zhang, Z., Chen, P. ... Zhuang, J. (2017). Tetramethylpyrazine-mediated regulation of CXCR4 in retinoblastoma is sensitive to cell density. Molecular Medicine Reports, 15, 2481-2488. https://doi.org/10.3892/mmr.2017.6293
MLA
Wu, N., Xu, L., Yang, Y., Yu, N., Zhang, Z., Chen, P., Zhang, J., Tang, M., Yuan, M., Ge, J., Yu, K., Zhuang, J."Tetramethylpyrazine-mediated regulation of CXCR4 in retinoblastoma is sensitive to cell density". Molecular Medicine Reports 15.5 (2017): 2481-2488.
Chicago
Wu, N., Xu, L., Yang, Y., Yu, N., Zhang, Z., Chen, P., Zhang, J., Tang, M., Yuan, M., Ge, J., Yu, K., Zhuang, J."Tetramethylpyrazine-mediated regulation of CXCR4 in retinoblastoma is sensitive to cell density". Molecular Medicine Reports 15, no. 5 (2017): 2481-2488. https://doi.org/10.3892/mmr.2017.6293