Department of Second Dental Center, Peking University School and Hospital of Stomatology, Beijing 100101, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Traditional Chinese Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Anticancer Agents Med Chem. 2022 Aug 4;22(15):2799-2806. doi: 10.2174/1871520622666220324105435.
Oral squamous cell carcinoma (OSCC) is a rampant cancer type in head and neck cancers with a poor prognosis and a high recurrence rate. Eugenol shows an anticancer effect in a variety of cancers, but it has been rarely studied in oral squamous cell carcinoma (OSCC).
The purpose of this study was to explore the role of Eugenol in OSCC and the underlying mechanism.
After different concentrations of Eugenol (0, 200, 400, and 800 μM) treatment, the viability, proliferation, migration, and invasion of OSCC cell line SCC9 were measured by CCK-8, colony formation, wound-healing, and transwell assays, respectively. TUNEL staining was employed to detect apoptosis. Western blotting was used to evaluate gene expression at the protein level. Molecular docking was used to identify the target of Eugenol.
Eugenol decreased the proliferation and reduced the abilities of invasion and migration along with the expression of matrix metalloproteinases (MMP) 2 and MMP9 in SCC9 cells. On the contrary, the ratio of apoptotic cells was increased by Eugenol. In addition, Eugenol down-regulated B cell lymphoma-2 (Bcl-2) expression, but up-regulated BCL-2 associated X (Bax), cleaved caspase 3, and cleaved poly-ADP ribose polymerase (PARP) expression. Meanwhile, Eugenol exerted its effect on SCC9 cells in a concentration-dependent manner. Eugenol could bind to macrophage migration inhibitory factor (MIF), the expression of which was down-regulated after Eugenol treatment. Besides, overexpression of MIF reversed all the effects of Eugenol on OSCC cells.
In summary, Eugenol suppressed the malignant processes of OSCC cells by targeting MIF, which could guide the clinical application of Eugenol in OSCC.
口腔鳞状细胞癌(OSCC)是头颈部癌症中一种猖獗的癌症类型,预后不良,复发率高。丁香酚在多种癌症中表现出抗癌作用,但在口腔鳞状细胞癌(OSCC)中研究甚少。
本研究旨在探讨丁香酚在 OSCC 中的作用及其潜在机制。
用不同浓度的丁香酚(0、200、400 和 800μM)处理后,通过 CCK-8、集落形成、划痕愈合和 Transwell 检测分别测量 OSCC 细胞系 SCC9 的活力、增殖、迁移和侵袭。TUNEL 染色检测细胞凋亡。Western blot 检测蛋白水平的基因表达。分子对接鉴定丁香酚的靶标。
丁香酚降低 SCC9 细胞的增殖能力,并降低其侵袭和迁移能力,同时降低基质金属蛋白酶(MMP)2 和 MMP9 的表达。相反,丁香酚增加了细胞凋亡的比例。此外,丁香酚下调 B 细胞淋巴瘤-2(Bcl-2)的表达,但上调 BCL-2 相关 X(Bax)、裂解的 caspase 3 和裂解的多聚 ADP 核糖聚合酶(PARP)的表达。同时,丁香酚以浓度依赖的方式对 SCC9 细胞发挥作用。丁香酚可以与巨噬细胞移动抑制因子(MIF)结合,用丁香酚处理后 MIF 的表达下调。此外,MIF 的过表达逆转了丁香酚对 OSCC 细胞的所有作用。
综上所述,丁香酚通过靶向 MIF 抑制 OSCC 细胞的恶性进程,为丁香酚在 OSCC 中的临床应用提供了指导。