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橄榄苦苷通过 TGF-β1 信号通路抑制头颈部鳞状细胞癌的侵袭。

Oleuropein inhibits invasion of squamous cell carcinoma of the head and neck through TGF-β1 signaling pathway.

机构信息

Department of Otolaryngology, Wuxi Second Clinical Medical College of Nantong University, No. 68, Zhongshan Road, Liangxi District, Wuxi, Jiangsu, 214002, People's Republic of China.

出版信息

BMC Cancer. 2022 Sep 1;22(1):942. doi: 10.1186/s12885-022-09979-2.

DOI:10.1186/s12885-022-09979-2
PMID:36050634
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9434901/
Abstract

BACKGROUND

Squamous cell carcinoma of the head and neck (SCCHN) is globally the sixth most common cancer. TGF-β1 is a key regulator of cell proliferation and differentiation, and it induces the epithelial-mesenchymal transition (EMT) by activating Smad2 signaling in SCCHN cells. Previous studies have revealed that oleuropein (OL) can inhibit the EMT alterations and migration of cancer cells. The aim of this study was to examine the involvement of TGF-β1 signaling pathway in SCCHN and the effect of OL on it.

METHODS

Through in vitro experiments at cellular level and in vivo evaluation in mouse xenograft tumor model, with morphological and Western blotting assays, we examined the effects of OL on TGF-β1-mediated signaling pathway in Tu686, CAL-27 and 686LN-M2 tumor cell lines.

RESULTS

We found that OL reversed the TGF-β1-induced EMT, and changed the morphology of cells and the expression levels of epithelial and interstitial markers. Wound-healing and transwell invasion assays indicated that OL reversed the TGF-β1-promoted cell migration and invasion dramatically. The effects of OL were also verified in xenograft tumor model of mice, and the findings were identical to the in vitro assays.

CONCLUSION

This study demonstrated that OL inhibits the growth and metastasis of SCCHN by interfering with the TGF-β1 signaling pathway, and the findings are beneficial for the development of prevention and treatment strategy of SCCHN. Due to the low toxicity and less side effects, OL may be of potential value in the inhibition of metastasis of SCCHN and improve survival.

摘要

背景

头颈部鳞状细胞癌（SCCHN）是全球第六大常见癌症。TGF-β1 是细胞增殖和分化的关键调节剂，它通过激活 SCCHN 细胞中的 Smad2 信号诱导上皮-间充质转化（EMT）。先前的研究表明，橄榄苦苷（OL）可以抑制 EMT 改变和癌细胞的迁移。本研究旨在研究 TGF-β1 信号通路在 SCCHN 中的作用以及 OL 对其的影响。

方法

通过体外细胞实验和小鼠异种移植肿瘤模型的体内评估，采用形态学和 Western blot 检测，研究 OL 对 Tu686、CAL-27 和 686LN-M2 肿瘤细胞系中 TGF-β1 介导的信号通路的影响。

结果

我们发现 OL 逆转了 TGF-β1 诱导的 EMT，并改变了细胞形态和上皮及间质标志物的表达水平。划痕愈合和 Transwell 侵袭实验表明，OL 显著逆转了 TGF-β1 促进的细胞迁移和侵袭。OL 在小鼠异种移植肿瘤模型中的作用也得到了验证，结果与体外实验一致。

结论

本研究表明，OL 通过干扰 TGF-β1 信号通路抑制 SCCHN 的生长和转移，这一发现有助于开发 SCCHN 的预防和治疗策略。由于 OL 毒性低、副作用小，OL 可能在抑制 SCCHN 转移和提高生存率方面具有潜在价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/bccb12743b9a/12885_2022_9979_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/4dbde73fb0db/12885_2022_9979_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/483a74554af9/12885_2022_9979_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/e2c563e76205/12885_2022_9979_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/c390a48d9992/12885_2022_9979_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/fd16e5805a24/12885_2022_9979_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/4cfb4d8f7906/12885_2022_9979_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/2c89d6f8b436/12885_2022_9979_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/1119047fa4df/12885_2022_9979_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/bccb12743b9a/12885_2022_9979_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/4dbde73fb0db/12885_2022_9979_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/483a74554af9/12885_2022_9979_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/e2c563e76205/12885_2022_9979_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/c390a48d9992/12885_2022_9979_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/fd16e5805a24/12885_2022_9979_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/4cfb4d8f7906/12885_2022_9979_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/2c89d6f8b436/12885_2022_9979_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/1119047fa4df/12885_2022_9979_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c0/9434901/bccb12743b9a/12885_2022_9979_Fig9_HTML.jpg

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