PPT1 Reduction Contributes to Erianin-Induced Growth Inhibition in Oral Squamous Carcinoma Cells.
PPT1 Reduction Contributes to Erianin-Induced Growth Inhibition in Oral Squamous Carcinoma Cells.
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PPT1 减少有助于毛兰素诱导的口腔鳞状癌细胞生长抑制
DOI：
10.3389/fcell.2021.764263
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Chen F
中科院分区：
文献类型：
--
作者：
Luo Q;Li X;Gan G;Yang M;Chen X;Chen F
毛兰素的抗癌特性最近被发现。然而，毛兰素在口腔鳞状细胞癌（OSCC）中的抗肿瘤作用尚不清楚。在这项研究中，我们证明毛兰素可以阻碍口腔鳞状细胞癌细胞的生长在体外和体内。毛兰素可诱导OSCC细胞发生明显的G2/M期阻滞、凋亡和Gasdermin E（GSDME）依赖的细胞凋亡。此外，毛兰素增加自噬体的形成，但减少自溶酶体功能。进一步的研究表明毛兰素显著抑制蛋白棕榈酰硫酯酶1（PPT 1）和mTOR信号的表达。据报道，PPT 1通过调节自噬和mTOR信号传导而成为癌症进展的关键调节因子。根据在线数据库，在OSCC组织中观察到较高的PPT 1表达，并且与较差的患者预后相关。由于PPT 1过表达显著逆转毛兰素诱导的OSCC细胞生长抑制，我们确定了PPT 1减少在毛兰素诱导的生长抑制中的重要性。利用异种移植瘤模型，证实毛兰素的体内抗肿瘤作用。毛兰素有效地减小了肿瘤的大小，同时明显降低了异种移植肿瘤组织中PPT 1的表达和mTOR的磷酸化。因此，本研究表明毛兰素可能用于口腔鳞癌的治疗。
The anticancer properties of erianin have been recently discovered. However, the antitumor effect of erianin in oral squamous cell carcinoma (OSCC) remains unclear. In this study, we demonstrated that erianin can hamper OSCC cells growth both in vitro and in vivo. Erianin induced obvious G2/M arrest as well as apoptosis and gasdermin E (GSDME)-dependent pyroptosis in OSCC cells. Moreover, erianin increased autophagosome formation but decreased autolysosome function. Further study indicated that erianin significantly suppressed the expression of protein-palmitoyl thioesterase 1 (PPT1) and mTOR signaling. PPT1 has been reported to be a critical regulator of cancer progression by its modulation of autophagy and mTOR signaling. According to online databases, higher expression of PPT1 has been observed in OSCC tissues and is associated with poorer patient prognosis. As overexpression of PPT1 significantly reversed erianin-induced growth inhibition in OSCC cells, we identified the importance of PPT1 reduction in erianin-induced growth suppression. With the xenograft model, we confirmed the antitumor effect of erianin in vivo. Erianin efficiently decreased the tumor sizes, together with visibly reduced expression of PPT1 and phosphorylation of mTOR in the xenograft tumor tissues. Therefore, the present study indicated that erianin may be potentially used in OSCC therapy.
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DOI：
10.1038/s41573-021-00154-z
发表时间：
2021-05
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Liu X;Xia S;Zhang Z;Wu H;Lieberman J
通讯作者：
Lieberman J
影响因子：
6
作者：
Niklaus NJ;Tokarchuk I;Zbinden M;Schläfli AM;Maycotte P;Tschan MP
通讯作者：
Tschan MP
影响因子：
4.7
作者：
Coronel-Hernández J;Salgado-García R;Cantú-De León D;Jacobo-Herrera N;Millan-Catalan O;Delgado-Waldo I;Campos-Parra AD;Rodríguez-Morales M;Delgado-Buenrostro NL;Pérez-Plasencia C
通讯作者：
Pérez-Plasencia C
免疫检查点抑制剂联合化疗与传统化疗治疗复发性或转移性头颈鳞状细胞癌的比较：系统评价和网络荟萃分析
影响因子：
4.9
作者：
Jin Z;Zhang B;Zhang L;Huang W;Mo X;Chen Q;Wang F;Chen Z;Li M;Zhang S
通讯作者：
Zhang S
影响因子：
39.3
作者：
Chen, Peng;Wu, Qibiao;Sui, Xinbing
通讯作者：
Sui, Xinbing