Anti-tumor effect of AZD8055 against neuroblastoma cells in vitro and in vivo

被引：23

作者：

Xu, Dong-Qing ^{[1
]}

Toyoda, Hidemi ^{[1
]}

Yuan, Xiao-Jun ^{[2
]}

Qi, Lei ^{[1
]}

Chelakkot, Vipin Shankar ^{[1
]}

Morimoto, Man ^{[1
]}

Hanaki, Ryo ^{[1
]}

Kihira, Kentarou ^{[1
]}

Hori, Hiroki ^{[1
]}

Komada, Yoshihiro ^{[1
]}

Hirayama, Masahiro ^{[1
]}

机构：

[1] Mie Univ, Grad Sch Med, Dept Pediat, 2-174 Edobashi, Tsu, Mie, Japan

[2] Shanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Dept Pediat Hematol Oncol, Shanghai 200092, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2018年 / 365卷 / 02期

关键词：

Neuroblastoma; mTOR kinase; Autophagy; Apoptosis; AZD8055; TARGETING MTOR; PI3K/AKT/MTOR PATHWAY; MAMMALIAN TARGET; CANCER; INHIBITOR; THERAPY; GROWTH; AUTOPHAGY; RATIONALE; POTENT;

D O I：

10.1016/j.yexcr.2018.02.032

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Neuroblastoma (NB) is one of the most common solid tumors in children. High-risk NB remains lethal in about 50% of patients despite comprehensive and intensive treatments. Activation of PI3K/Akt/mTOR signaling pathway correlates with oncogenesis, poor prognosis and chemotherapy resistance in NB. Due to its central role in growth and metabolism, mTOR seems to be an important factor in NB, making it a possible target for NB. In this study, we investigated the effect of AZD8055, a potent dual mTORC1-mTORC2 inhibitor, in NB cell lines. Our data showed that mTOR signaling was extensively activated in NB cells. The activity of mTOR and downstream molecules were down-regulated in AZD8055-treated NB cells. Significantly, AZD8055 effectively inhibited cell growth and induced cell cycle arrest, autophagy and apoptosis in NB cells. Moreover, AZD8055 significantly reduced tumor growth in mice xenograft model without apparent toxicity. Taken together, our results highlight the potential of mTOR as a promising target for NB treatment. Therefore, AZD8055 may be further investigated for treatment in clinical trials for high risk NB.

引用

页码：177 / 184

页数：8

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