当前位置： SCI文献检索 > Molecular Medicine Reports期刊下所有文献 > 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.

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.

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 comple-tely 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 inhi-bitor into TBMS1‑treated NCI‑H1299 cells. Vascular endo-thelial 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.

journal_name

Mol Med Rep

journal_title

Molecular medicine reports

authors

Shi H,Bi H,Sun X,Dong H,Jiang Y,Mu H,Liu G,Kong W,Gao R,Su J

doi

10.3892/mmr.2018.8459

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

4327-4336

issue

eissn

1791-2997

issn

1791-3004

journal_volume

pub_type

杂志文章

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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.