Division of Surgery, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan, R.O.C.
Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan, R.O.C.
Anticancer Res. 2021 Dec;41(12):6095-6104. doi: 10.21873/anticanres.15429.
BACKGROUND/AIM: This study investigated the anti-metastatic effects of cetyltrimethylammonium bromide (CTAB) on tongue squamous cell carcinoma (TSCC) SCC4 cells.
Cell morphology, viability, cell cycle distribution, adhesion, migration, invasion and the expression levels of associated proteins were examined using microscopy, WST-1, wound-healing, Boyden chamber assays, and western blotting, respectively.
CTAB significantly affected SCC4 cell morphology from spindle-shaped to cobblestone-shaped and resulted in loss of adherence. CTAB significantly inhibited cell adhesion, migration, and invasion of SCC4 cells, independent of cell viability. CTAB reduced expression of matrix metalloproteinases (MMPs) such as MMP3, MMP7, and MMP14 in a concentration-dependent manner, while it increased expression of tissue inhibitors of metalloproteinase 3 (TIMP3). In addition, CTAB reduced the phosphorylation of mothers against decapentaplegic homolog 2/3 (Smad2/3) proteins, which mediated CTAB-inhibited migration and invasion in SCC4 cells. These effects were reversed by TGF-β1.
CTAB attenuates the mesenchymal characteristics through upregulation of TIMP3 by inhibiting the canonical TGF-β/Smad/miR-181b/TIMP3 signaling involved in extracellular matrix remodeling in SCC4 cells and might be a promising anti-metastatic therapeutic agent for TSCC.
背景/目的：本研究旨在探讨十六烷基三甲基溴化铵（CTAB）对舌鳞状细胞癌（TSCC）SCC4 细胞的抗转移作用。
通过显微镜观察、WST-1 法、划痕愈合试验、Boyden 室测定和 Western blot 分析，分别检测细胞形态、活力、细胞周期分布、黏附、迁移和侵袭以及相关蛋白的表达水平。
CTAB 显著影响 SCC4 细胞形态，使其从梭形变为鹅卵石形，并导致细胞黏附丧失。CTAB 显著抑制 SCC4 细胞的黏附、迁移和侵袭，且与细胞活力无关。CTAB 呈浓度依赖性降低基质金属蛋白酶（MMPs）如 MMP3、MMP7 和 MMP14 的表达，同时增加组织金属蛋白酶抑制剂 3（TIMP3）的表达。此外，CTAB 降低了介导 CTAB 抑制 SCC4 细胞迁移和侵袭的母系抗 décapentaplegic 同源物 2/3（Smad2/3）蛋白的磷酸化。这些作用可被 TGF-β1 逆转。
CTAB 通过抑制细胞外基质重塑过程中的经典 TGF-β/Smad/miR-181b/TIMP3 信号通路，上调 TIMP3，从而减弱 SCC4 细胞的间充质特征，可能成为治疗 TSCC 的有前途的抗转移治疗剂。
