Regulatory roles of OASL in lung cancer cell sensitivity to Actinidia chinensis Planch root extract (acRoots)

Regulatory roles of OASL in lung cancer cell sensitivity to Actinidia chinensis Planch root extract (acRoots)
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DOI:
10.1007/s10565-018-9422-4
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发表时间:
2018-06-01
影响因子:
6.1
通讯作者:
Wang, Xiangdong
Wang, Xiangdong
中科院分区:
医学2区
文献类型:
--
作者:
Lv, Jiapei;Wang, Lingyan;Wang, Xiangdong

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肺癌是世界上最常见的恶性肿瘤之一。中华猕猴桃根提取物(Actinidia chinensis Planch root extract,acRoots)具有抗肿瘤作用,但其分子机制尚不清楚。本研究旨在探讨肺癌细胞感受acRoots抑制作用的分子机制,特别关注免疫相关基因谱。我们首次提供了acRoots通过PI 3 K-OASL信号通路显著抑制肺癌细胞增殖和凋亡的临床前证据。用不同剂量的acRoots处理后,检测肺癌细胞类型的免疫相关基因谱的异质性改变。OASL基因被鉴定为acRoots处理的肺癌细胞分子网络中的关键调节因子,并得到验证。OASL基因在肺癌细胞对acRoots的敏感性调节中起重要作用,该作用受PI 3 K信号通路的调节。因此,我们的数据表明,OASL可以是维持肺癌细胞对acRoots敏感性的决定性调节因子之一,并可能与耐药性的发展有关。OASL的调节可以是在癌症治疗期间改善药物疗效的替代策略。
Lung cancer is one of the most common malignancies worldwide. Actinidia chinensis Planch root extract (acRoots) was found to have the capacity of the anti-tumor, although the molecular mechanisms remain unclear. The present study aims to investigate the molecular mechanisms by which lung cancer cells sense to inhibitory effects of acRoots with a special focus on immune-associated gene profiles. We firstly provide a preclinical evidence that acRoots can significantly inhibit lung cancer cell proliferation and apoptosis via the PI3K-OASL signal pathway. The heterogeneous alterations of immune-associated gene profiles of lung cancer cell types were measured after treatment with various doses of acRoots. The OASL gene was identified as the key regulator in molecular networks of acRoots-treated lung cancer cells and validated. The OASL gene plays an important role in the regulation of lung cancer cell sensitivity to acRoots, which modulated by the PI3K signal pathway. Thus, our data indicate that OASL can be one of the decisive regulators to maintain lung cancer cell susceptibility to acRoots and may be associated with the development of drug resistance. The regulation of OASL can be an alternative strategy to improve drug efficacy during cancer therapies.