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Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway

  • Authors:
    • Hanbing Shi
    • Hongxia Bi
    • Xingyuan Sun
    • Haiying Dong
    • Yunfei Jiang
    • Haijun Mu
    • Guohua Liu
    • Weili Kong
    • Ruizhi Gao
    • Jiang Su
  • View Affiliations / Copyright

    Affiliations: Department of Respiration II, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Respiratory Medicine, The Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Neurology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Laboratory Center of Ultrastructural Pathology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Cardiovascular Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China
    Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4327-4336
    |
    Published online on: January 18, 2018
       https://doi.org/10.3892/mmr.2018.8459
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Abstract

Tubeimoside-1 (TBMS1), a triterpenoid saponin isolated from the tuber of Bolbostemma paniculatum (Maxim) Franquet, serves an universal suppressive role in multiple cancer types, including lung cancer. However, the mechanism involved in non‑small cell lung cancer (NSCLC) cells by which TBMS1 elicits its antitumor effects is not yet comple­tely understood. The present study indicated that 10 µmol/l TBMS1 significantly enhanced apoptosis and notably blocked the migration and invasion of NCI‑H1299 cells. These effects were reversed following transfection with miR‑126‑5p inhi­bitor into TBMS1‑treated NCI‑H1299 cells. Vascular endo­thelial growth factor-A (VEGF‑A) is a target gene for miR‑126‑5p. Notably, results suggested that the downregulated VEGF‑A and VEGFR‑2 in TBMS1‑treated NCI‑H1299 cells were upregulated after inhibiting miR‑126‑5p, and overexpression of VEGF‑A or VEGFR‑2 could significantly reduce apoptosis and promote the migration and invasion of TBMS1‑treated NCI‑H1299 cells. Furthermore, TBMS1 combined with TBHQ (an ERK activator) dramatically suppressed TBMS1‑induced apoptosis and stimulated TBMS1‑reduced migration and invasion in NCI‑H1299 cells, suggesting that TBMS1 inhibits the ERK signaling pathway and represses the growth and metastasis of NCI‑H1299 cells. Further study demonstrated that either inhibiting miR‑126‑5p or overexpressing VEGF‑A and VEGFR‑2 in TBMS1‑treated NCI‑H1299 cells elevated the mRNA expression levels and phosphorylation levels of MEK1, as well as ERK. To conclude, TBMS1 increases miR‑126‑5p expression, whereas overexpressing miR‑126‑5p inactivates VEGF‑A/VEGFR‑2/ERK signaling pathway, which ultimately actuates the pro‑apoptotic and anti‑metastatic effects in NCI‑H1299 cells. Therefore, the present findings provide a theoretical foundation for TBMS1 as a potential candidate in NSCLC treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Shi H, Bi H, Sun X, Dong H, Jiang Y, Mu H, Liu G, Kong W, Gao R, Su J, Su J, et al: Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway. Mol Med Rep 17: 4327-4336, 2018.
APA
Shi, H., Bi, H., Sun, X., Dong, H., Jiang, Y., Mu, H. ... Su, J. (2018). Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway. Molecular Medicine Reports, 17, 4327-4336. https://doi.org/10.3892/mmr.2018.8459
MLA
Shi, H., Bi, H., Sun, X., Dong, H., Jiang, Y., Mu, H., Liu, G., Kong, W., Gao, R., Su, J."Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway". Molecular Medicine Reports 17.3 (2018): 4327-4336.
Chicago
Shi, H., Bi, H., Sun, X., Dong, H., Jiang, Y., Mu, H., Liu, G., Kong, W., Gao, R., Su, J."Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway". Molecular Medicine Reports 17, no. 3 (2018): 4327-4336. https://doi.org/10.3892/mmr.2018.8459
Copy and paste a formatted citation
x
Spandidos Publications style
Shi H, Bi H, Sun X, Dong H, Jiang Y, Mu H, Liu G, Kong W, Gao R, Su J, Su J, et al: Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway. Mol Med Rep 17: 4327-4336, 2018.
APA
Shi, H., Bi, H., Sun, X., Dong, H., Jiang, Y., Mu, H. ... Su, J. (2018). Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway. Molecular Medicine Reports, 17, 4327-4336. https://doi.org/10.3892/mmr.2018.8459
MLA
Shi, H., Bi, H., Sun, X., Dong, H., Jiang, Y., Mu, H., Liu, G., Kong, W., Gao, R., Su, J."Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway". Molecular Medicine Reports 17.3 (2018): 4327-4336.
Chicago
Shi, H., Bi, H., Sun, X., Dong, H., Jiang, Y., Mu, H., Liu, G., Kong, W., Gao, R., Su, J."Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway". Molecular Medicine Reports 17, no. 3 (2018): 4327-4336. https://doi.org/10.3892/mmr.2018.8459
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