New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer

  • Authors:
    • Sheng-Qi Wang
    • Bo-Xin Zhao
    • Yuan Liu
    • Ya-Tian Wang
    • Qian-Ying Liang
    • Yun Cai
    • Yun-Qi Zhang
    • Jiang-Hong Yang
    • Zhi-Hua Song
    • Guo-Feng Li
  • View Affiliations

  • Published online on: February 4, 2016     https://doi.org/10.3892/ijo.2016.3375
  • Pages: 1353-1360
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Abstract

Small cell lung cancer (SCLC) remains one of the most aggressive tumors with a poor prognosis. The clinical outcome of SCLC patients has reached its plateau with the existing standard treatment and thus new therapies are urgently required. Accumulating evidences have indicated that doxycycline, a commonly used antibiotic, has antitumor activity against several malignancies. However, whether doxycycline has antitumor activity in SCLC and its underlying mechanisms remain unclear. Our investigation demonstrated that doxycycline could significantly inhibit the proliferation and colony formulation of SCLC cells (p<0.05). Furthermore, both Hoechst 33258 dye staining and TUNEL assays indicated that doxycycline could induce remarkable apoptosis of H446 cells in a concentration-dependent manner. RT-PCR and western blot assays proved that apoptosis induction effect of doxycycline was achieved via inducing the expression of caspase-3 and bax, as well as attenuating the expression of survivin and bcl-2. Moreover, the wound healing assay and Transwell assay indicated that doxycycline could significantly suppress the migration and invasion of H446 cells in a concentration-dependent manner (p<0.05). ELISA assay proved that the inhibitory effect of doxycycline on the migration and invasion of H446 cells was achieved via decreasing the secretion of MMP-2, MMP-9 and VEGF, as well as increasing the secretion of TIMP-2. Taken together, doxycycline dose-dependently suppressed the proliferation, colony formulation, migration and invasion of SCLC cells, as well as induced apoptosis. These findings encourage further investigations on the potential of doxycycline as a candidate drug for the treatment of SCLC.

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April 2016
Volume 48 Issue 4

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

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APA
Wang, S., Zhao, B., Liu, Y., Wang, Y., Liang, Q., Cai, Y. ... Li, G. (2016). New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer. International Journal of Oncology, 48, 1353-1360. https://doi.org/10.3892/ijo.2016.3375
MLA
Wang, S., Zhao, B., Liu, Y., Wang, Y., Liang, Q., Cai, Y., Zhang, Y., Yang, J., Song, Z., Li, G."New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer". International Journal of Oncology 48.4 (2016): 1353-1360.
Chicago
Wang, S., Zhao, B., Liu, Y., Wang, Y., Liang, Q., Cai, Y., Zhang, Y., Yang, J., Song, Z., Li, G."New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer". International Journal of Oncology 48, no. 4 (2016): 1353-1360. https://doi.org/10.3892/ijo.2016.3375