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

Shi,Hanbing; Bi,Hongxia; Sun,Xingyuan; Dong,Haiying; Jiang,Yunfei; Mu,Haijun; Liu,Guohua; Kong,Weili; Gao,Ruizhi; Su,Jiang

doi:10.3892/mmr.2018.8459

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
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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
Published online on: January 18, 2018 https://doi.org/10.3892/mmr.2018.8459
Pages: 4327-4336
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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