Tetramethylpyrazine inhibits tumor growth of lung cancer through disrupting angiogenesis via BMP/Smad/Id-1 signaling

  • Authors:
    • Youchao Jia
    • Zhigang Wang
    • Aimin Zang
    • Shunchang Jiao
    • Sumei Chen
    • Yan Fu
  • View Affiliations

  • Published online on: March 15, 2016     https://doi.org/10.3892/ijo.2016.3443
  • Pages: 2079-2086
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Abstract

The underlying mechanisms of inhibitory effects induced by tetramethylpyrazine (TMP) on angiogenesis and tumor growth of lung cancer were investigated. In vitro cell proliferation, migration, and tube formation of human microvascular endothelial cells (HMEC-1) were evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide (MTT), wound healing, Transwell, and Matrigel assays. The expression of BMP/Smad/Id-1 signals was detected by RT-PCR and western blotting. In an A549 xenograft tumor model, TMP (40 and 80 mg/kg/day) was intraperitoneally injected into mice. The expressions of CD31, phosphorylated Smad1/5/8, and Id-1 were measured by immunohistochemistry. We demonstrated that TMP inhibited proliferation, migration, and capillary tube formation of HMEC-1 in a dose- and time-dependent manner. Furthermore, treatment of HMEC-1 cells with TMP (0.4 mg/ml) significantly upregulated BMP2 expression and downregulated BMPRIA, BMPRII, phosphorylated Smad1/5/8, and Id-1 expression. In addition, administrations of TMP remarkably inhibited tumor growth of A549 xenograft in nude mice. The CD31, phosphorylated Smad1/5/8, and Id-1 expression were significantly inhibited in TMP-treated xenograft tumors compared with the vehicle. In conclusion, our results indicated that TMP suppressed angiogenesis and tumor growth of lung cancer via blocking the BMP/Smad/Id-1 signaling.
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May-2016
Volume 48 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Jia Y, Wang Z, Zang A, Jiao S, Chen S and Fu Y: Tetramethylpyrazine inhibits tumor growth of lung cancer through disrupting angiogenesis via BMP/Smad/Id-1 signaling. Int J Oncol 48: 2079-2086, 2016
APA
Jia, Y., Wang, Z., Zang, A., Jiao, S., Chen, S., & Fu, Y. (2016). Tetramethylpyrazine inhibits tumor growth of lung cancer through disrupting angiogenesis via BMP/Smad/Id-1 signaling. International Journal of Oncology, 48, 2079-2086. https://doi.org/10.3892/ijo.2016.3443
MLA
Jia, Y., Wang, Z., Zang, A., Jiao, S., Chen, S., Fu, Y."Tetramethylpyrazine inhibits tumor growth of lung cancer through disrupting angiogenesis via BMP/Smad/Id-1 signaling". International Journal of Oncology 48.5 (2016): 2079-2086.
Chicago
Jia, Y., Wang, Z., Zang, A., Jiao, S., Chen, S., Fu, Y."Tetramethylpyrazine inhibits tumor growth of lung cancer through disrupting angiogenesis via BMP/Smad/Id-1 signaling". International Journal of Oncology 48, no. 5 (2016): 2079-2086. https://doi.org/10.3892/ijo.2016.3443