دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Anti-tumor effect of AZD8055 against neuroblastoma cells in vitro and in vivo.
المؤلفون: Xu, Dong-Qing1, Toyoda, Hidemi1, Yuan, Xiao-Jun2, Qi, Lei1, Chelakkot, Vipin Shankar1, Morimoto, Mari1, Hanaki, Ryo1, Kihira, Kentarou1, Hori, Hiroki1, Komada, Yoshihiro1, Hirayama, Masahiro1 hirayama@clin.medic.mie-u.ac.jp
المصدر: Experimental Cell Research. Apr2018, Vol. 365 Issue 2, p177-184. 8p.
مصطلحات موضوعية: *NEUROBLASTOMA, *ANTINEOPLASTIC agents, *NEOPLASTIC cell transformation, *CANCER chemotherapy, *TUMOR growth, *THERAPEUTICS
مستخلص: 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. [ABSTRACT FROM AUTHOR]
قاعدة البيانات: Academic Search Index
الوصف
تدمد:00144827
DOI:10.1016/j.yexcr.2018.02.032