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淫羊藿苷通过抑制Toll样受体4和NF-κB P65磷酸化减轻人口腔鳞状细胞癌的生长和侵袭能力。

Icariin Mitigates the Growth and Invasion Ability of Human Oral Squamous Cell Carcinoma via Inhibiting Toll-Like Receptor 4 and Phosphorylation of NF-κB P65.

作者信息

Lei Ke, Ma Bing, Shi Ping, Jin Che, Ling Tan, Li Longjiang, He Xiangyi, Wang Lunchang

机构信息

Department of Stomatology, Central Hospital of Guangyuan, Guangyuan 628000, People's Republic of China.

Department of Respiratory, Central Hospital of Guangyuan, Guangyuan 628000, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Jan 10;13:299-307. doi: 10.2147/OTT.S214514. eCollection 2020.

Abstract

BACKGROUND

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy worldwide. Icariin (ICA), an active ingredient of flavonoids, has been demonstrated to possess antitumor activity in diverse cancers. Whereas, the role of ICAin OSCC is still unclear.

METHODS

Herein, we investigated the anti-tumor effects of ICA in vitro and in vivo. CCK-8, colony formation and trans-well assay were used to examined viability, proliferation and invasion in SCC-9 and SCC-15 cell lines, respectively. Next, we tested the expression of toll-like receptor 4 (TLR4) and NF-κB P65 by western blot or immunofluorescence staining. Finally, we constructed a xenograft mice model to investigate the effect of ICA in vivo.

RESULTS

In vitro, ICA decreased the human oral squamous cells viability, proliferation and invasion in a concentration-dependent manner. Besides, ICA decreased the phosphorylation level of P65 and down-regulated TLR4 protein. In vivo, compared with control, ICA significantly suppressed the tumor size and weight. In addition, ICA downregulated the levels of Ki67 and VEGF markedly. Dramatically, ICA decreased the phosphorylation level of P65 in tumor tissues.

CONCLUSION

Taken together, ICA could act as a anticancer drug against OSCC to mitigate the growth and invasion ability, the underlying mechanism may due to the down-regulation of TLR4/NF-κB signaling.

摘要

背景

口腔鳞状细胞癌(OSCC)是一种在全球范围内具有侵袭性的恶性肿瘤。淫羊藿苷(ICA)是黄酮类化合物的一种活性成分,已被证明在多种癌症中具有抗肿瘤活性。然而,ICA在OSCC中的作用仍不清楚。

方法

在此,我们研究了ICA在体外和体内的抗肿瘤作用。分别使用CCK-8、集落形成和Transwell实验检测SCC-9和SCC-15细胞系的活力、增殖和侵袭能力。接下来,我们通过蛋白质免疫印迹或免疫荧光染色检测Toll样受体4(TLR4)和NF-κB P65的表达。最后,我们构建了异种移植小鼠模型来研究ICA在体内的作用。

结果

在体外,ICA以浓度依赖性方式降低人口腔鳞状细胞的活力、增殖和侵袭能力。此外,ICA降低了P65的磷酸化水平并下调了TLR4蛋白表达。在体内,与对照组相比,ICA显著抑制了肿瘤大小和重量。此外,ICA明显下调了Ki67和VEGF的水平。引人注目的是,ICA降低了肿瘤组织中P65的磷酸化水平。

结论

综上所述,ICA可作为一种抗OSCC的抗癌药物,减轻其生长和侵袭能力,其潜在机制可能是由于TLR4/NF-κB信号通路的下调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a45/6971293/88340557be7d/OTT-13-299-g0001.jpg

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