Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan.
Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan.
Front Endocrinol (Lausanne). 2020 Sep 30;11:568436. doi: 10.3389/fendo.2020.568436. eCollection 2020.
Oral squamous cell carcinoma (OSCC) that comprises about 90% of all oral cancer cases is associated with poor prognosis due to its highly metastatic nature. The majority of OSCC treatment options are related detrimental side-effects. The present study aimed at deciphering the effects of a bioactive phytochemical, sodium danshensu, on human oral cancer cell metastasis. The treatment of FaDu and Ca9-22 cells with different doses of sodium danshensu (25, 50, and 100 μM) caused a significant reduction in cellular motility, migration, and invasion, as compared to the untreated cells. This effect was associated with a reduced expression of MMP-2, vimentin and N-cadherin, together with an enhanced expression of E-cadherin and ZO-1. Further investigation on the molecular mechanism revealed that treatment with sodium danshensu caused significant reduction in p38 phosphorylation; however, phosphorylation of ERK1/2 significantly decreased only in FaDu cells, whereas p-JNK1/2 did not show any alteration. A combination of p38 and JNK1/2 inhibitors with sodium danshensu also reduced the migration in the FaDu and Ca9-22 cell lines. Collectively, the present study findings reveal that sodium danshensu execute anti-metastatic effect by suppressing p38 phosphorylation in human oral cancer. The study identifies sodium danshensu as a potential natural anticancer agent that can be used therapeutically to manage highly metastatic OSCC.
口腔鳞状细胞癌（OSCC）约占所有口腔癌病例的 90%，由于其高度转移性，预后较差。大多数 OSCC 治疗选择都与有害的副作用有关。本研究旨在探讨一种生物活性植物化学物质丹参酸钠对人口腔癌细胞转移的影响。与未处理的细胞相比，用不同剂量的丹参酸钠（25、50 和 100 μM）处理 FaDu 和 Ca9-22 细胞，可显著降低细胞迁移、迁移和侵袭能力。这种作用与 MMP-2、波形蛋白和 N-钙粘蛋白表达减少以及 E-钙粘蛋白和 ZO-1 表达增强有关。进一步的分子机制研究表明，丹参酸钠处理可显著降低 p38 磷酸化；然而，仅在 FaDu 细胞中 ERK1/2 的磷酸化显著降低，而 p-JNK1/2 没有发生任何变化。p38 和 JNK1/2 抑制剂与丹参酸钠联合使用也可减少 FaDu 和 Ca9-22 细胞系的迁移。总之，本研究结果表明，丹参酸钠通过抑制人口腔癌细胞中的 p38 磷酸化发挥抗转移作用。该研究确定丹参酸钠作为一种潜在的天然抗癌剂，可用于治疗高度转移性 OSCC。
