Thymoquinone Suppresses the Proliferation, Migration and Invasiveness through Regulating ROS, Autophagic Flux and miR-877-5p in Human Bladder Carcinoma Cells.

Thymoquinone Suppresses the Proliferation, Migration and Invasiveness through Regulating ROS, Autophagic Flux and miR-877-5p in Human Bladder Carcinoma Cells.
复制标题

百里醌通过调节人膀胱癌细胞中的 ROS、自噬流和 miR-877-5p 抑制增殖、迁移和侵袭

DOI:
10.7150/ijbs.60401
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发表时间:
2021
影响因子:
9.2
通讯作者:
Jin X
Jin X
中科院分区:
生物学2区
文献类型:
--
作者:
Zhou X;Wang F;Wu H;Chen X;Zhang Y;Lin J;Cai Y;Xiang J;He N;Hu Z;Jin X

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膀胱癌是世界上十大最常诊断的癌症类型之一。百里醌 (TQ) 作为一种植物化学活性代谢物,从黑种草 (Nigella sativa) 种子中提取,在多种疾病中具有多种生物学特性。而且,TQ突出的抗癌作用也越来越受到人们的关注。在某些情况下,适度的自噬被认为有助于恶性细胞适应不同的应激源。相反,据报道,与线粒体膜电位(MMP)损失密切相关,细胞内活性氧(ROS)的上调可激活许多癌症类型的细胞凋亡。此外,microRNA在癌细胞病理过程中的重要作用也已被前期研究所证实。目前的研究证实,TQ 通过激活膀胱癌细胞中 caspase 依赖性细胞凋亡来抑制生存、增殖、迁移和侵袭,这是由 TQ 诱导膀胱癌细胞中 ROS 增加介导的。此外,TQ被证明可以阻断自噬体和溶酶体的融合,导致自噬体的积累和随后的细胞凋亡。此外,TQ 还被发现启动 miR-877-5p/PD-L1 轴,从而抑制上皮间质转化 (EMT) 和膀胱癌细胞的侵袭。总的来说,TQ 通过上调 ROS 水平和削弱自噬通量来诱导细胞凋亡,并通过激活膀胱癌细胞中的 miR-877-5p/PD-L1 轴来抑制 EMT 和细胞侵袭。
Bladder carcinoma is among the top 10 most frequently diagnosed cancer types in the world. As a phytochemical active metabolic, thymoquinone (TQ) is extracted from seeds of Nigella sativa, possessing various biological properties in a wide range of diseases. Moreover, the outstanding anti-cancer effect of TQ is attracting increasing attentions. In certain circumstances, moderate autophagy is regarded to facilitate the adaptation of malignant cells to different stressors. Conversely, closely linked with the mitochondrial membrane potential (MMP) loss, the upregulation of intracellular reactive oxygen species (ROS) is reported to activate the cell apoptosis in many cancer types. Furthermore, the vital effects of microRNAs in the pathological processes of cancer cells have also been confirmed by previous studies. The present research confirms that TQ restrains the viability, proliferation, migration and invasion through activating caspase-dependent apoptosis in bladder carcinoma cells, which is mediated by TQ induced ROS increase in bladder carcinoma cells. Furthermore, TQ is proved to block the fusion of autophagosomes and lysosomes, causing the accumulation of autophagosomes and subsequent cell apoptosis. In addition, TQ is also found to initiate the miR-877-5p/PD-L1 axis, which suppresses the epithelial mesenchymal transition (EMT) and invasion of bladder carcinoma cells. Taken together, TQ induces the apoptosis through upregulating ROS level and impairing autophagic flux, and inhibiting the EMT and cell invasion via activating the miR-877-5p/PD-L1 axis in bladder carcinoma cells.
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