Zhou Chun-Li, Li Jing-Jing, Ji Peng
Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China (mainland).
Department of Ophthalmology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China (mainland).
Med Sci Monit. 2017 Jan 24;23:419-427. doi: 10.12659/msm.899732.
BACKGROUND This study was done to verify whether propofol could inhibit esophageal squamous cell carcinoma (ESCC) cell line EC9706 cell migration and invasion by targeting SOX4. MATERIAL AND METHODS Different concentrations of propofol were co-incubated with EC9706 cells. The pcDNA-SOX4 or SOX4 siRNA plasmid was transfected into cells before the treatment with propofol 5 µg/L. The migratory and invasion ability of EC9706 cells were tested by wound-healing assay and Transwell chambers. Western blotting was used to investigate the expressions of MMP-2, MMP-9, TIMP-1, TIMP-2, and SOX4. Gelatin zymography was employed to detect the activity of MMP2 and MMP-9. RESULTS Compared with the control, the migration and invasion activity of EC9706 cells were decreased after incubation with different concentrations of propofol (P<0.01). The expression of MMP-2, MMP-9, and SOX4 was decreased and that of TIMP-1 was increased in the propofol-treated EC9706 cells (P<0.01). Down-regulation of SOX4 by SOX4-siRNA had the same effect as propofol on EC9706 cells, including suppressing cell migration and invasion, inhibiting the expression and activity of MMP-2/9, and increasing the expression TIMP-1. Over-expression of SOX4 could partly abrogated propofol-mediated inhibition of EC9706 cell migration and invasion. CONCLUSIONS Propofol inhibits EC9706 cell migration and invasion by down-regulation of SOX4.
背景 本研究旨在验证丙泊酚是否可通过靶向SOX4抑制食管鳞状细胞癌（ESCC）细胞系EC9706细胞的迁移和侵袭。材料与方法 将不同浓度的丙泊酚与EC9706细胞共同孵育。在用5μg/L丙泊酚处理细胞之前，将pcDNA-SOX4或SOX4 siRNA质粒转染到细胞中。通过伤口愈合试验和Transwell小室检测EC9706细胞的迁移和侵袭能力。采用蛋白质免疫印迹法研究基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）、金属蛋白酶组织抑制因子-1（TIMP-1）、金属蛋白酶组织抑制因子-2（TIMP-2）和SOX4的表达。采用明胶酶谱法检测MMP2和MMP-9的活性。结果 与对照组相比，不同浓度丙泊酚孵育后EC9706细胞的迁移和侵袭活性降低（P<0.01）。丙泊酚处理的EC9706细胞中，MMP-2、MMP-9和SOX4的表达降低，TIMP-1的表达增加（P<0.01）。SOX4-siRNA下调SOX4对EC9706细胞的作用与丙泊酚相同，包括抑制细胞迁移和侵袭、抑制MMP-2/9的表达和活性以及增加TIMP-1的表达。SOX4的过表达可部分消除丙泊酚介导的对EC9706细胞迁移和侵袭的抑制作用。结论 丙泊酚通过下调SOX4抑制EC9706细胞的迁移和侵袭。
