TY - EJOU
AU - Yang, Peizhen
AU - Sun, Dezhong
AU - Jiang, Fei
TI - Ailanthone Promotes Human Vestibular Schwannoma Cell Apoptosis and Autophagy by Downregulation of miR-21
T2 - Oncology Research
PY - 2018
VL - 26
IS - 6
SN - 1555-3906
AB - Ailanthone (AIL) is a quassinoid isolated from the traditional Chinese medicinal herb Ailanthus altissima.
The antitumor activities of AIL have been reported in several cancers. The purpose of the present study was
to explore the effect of AIL on vestibular schwannomas (VSs). Various concentrations of AIL (0–1 µM) were
used to treat human primary VS cells, and then cell viability, proliferation, apoptosis, and autophagy were
assessed. Expression of miR-21 in VS cells was altered by miRNA transfection. The functional actions of AIL
on miR-21 dysregulated cells were also assessed. AIL significantly reduced the viability of VS cells, and the
IC50 value was 0.48±0.023 µM. In response to 0.6 µM AIL, BrdU+
cell rate and cyclin D1 expression were
reduced, apoptotic cell rate was increased, caspase 3 and caspase 9 were cleaved, Beclin-1 and LC3-II were
accumulated, and p62 was downregulated. miR-21 was lowly expressed in AIL-treated cells, and AIL-induced
apoptosis and autophagy were attenuated by miR-21 overexpression. In addition, AIL downregulated Ras and
Raf and deactivated MEK, ERK, mTOR, and p70S6K, while the downregulation and deactivation induced by
AIL were reversed by miR-21 overexpression. To conclude, AIL inhibited VS cell proliferation and induced
apoptosis and autophagy. The antitumor activities of AIL in VS cells were realized possibly via downregulation
of miR-21 and blocking the Ras/Raf/MEK/ERK and mTOR pathways.
KW - Vestibular schwannoma (VS); Ailanthone (AIL); miR-21; Apoptosis; Autophagy
DO - 10.3727/096504018X15149775533331