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双去甲氧基姜黄素通过体外影响 NF-κB 和 MMP-2、MMP-9 信号通路抑制人脑胶质母细胞瘤 GBM8401 细胞迁移和侵袭。

Bisdemethoxycurcumin suppresses human brain glioblastoma multiforme GBM 8401 cell migration and invasion via affecting NF-κB and MMP-2 and MMP-9 signaling pathway in vitro.

机构信息

Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.

Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.

出版信息

Environ Toxicol. 2022 Oct;37(10):2388-2397. doi: 10.1002/tox.23604. Epub 2022 Jun 23.

Abstract

Human glioblastoma (GBM) is one of the common cancer death in adults worldwide, and its metastasis will lead to difficult treatment. Finding compounds for future to develop treatment is urgent. Bisdemethoxycurcumin (BDMC), a natural product, was isolated from the rhizome of turmeric (Curcuma longa), which has been shown to against many human cancer cells. In the present study, we evaluated the antimetastasis activity of BDMC in human GBM cells. Cell proliferation, cell viability, cellular uptake, wound healing, migration and invasion, and western blotting were analyzed. Results indicated that BDMC at 1.5-3 μM significantly decreased the cell proliferation by MTT assay. BDMC showed the highest uptake by cells at 3 h. After treatment of BDMC at 12-48 h significantly inhibited cell motility in GBM 8401 cells by wound healing assay. BDMC suppressed cell migration and invasion at 24 and 48 h treatment by transwell chamber assay. BDMC significantly decreased the levels of proteins associated with PI3K/Akt, Ras/MEK/ERK pathways and resulted in the decrease in the expressions of NF-κB, MMP-2, MMP-9, and N-cadherin, leading to the inhibition of cell migration and invasion. These findings suggest that BDMC may be a potential candidate for the antimetastasis of human GBM cells in the future.

摘要

人胶质母细胞瘤(GBM)是全世界成年人癌症死亡的常见原因之一,其转移将导致治疗困难。寻找化合物用于未来开发治疗方法是当务之急。双去甲氧基姜黄素(BDMC)是一种天然产物,从姜黄(Curcuma longa)的根茎中分离出来,已被证明能对抗多种人类癌细胞。在本研究中,我们评估了 BDMC 在人 GBM 细胞中的抗转移活性。分析了细胞增殖、细胞活力、细胞摄取、划痕愈合、迁移和侵袭以及蛋白质印迹。结果表明,BDMC 在 1.5-3 μM 时通过 MTT 测定显著降低细胞增殖。BDMC 在 3 小时时对细胞的摄取最高。BDMC 处理 12-48 小时后,划痕愈合试验明显抑制 GBM 8401 细胞的细胞迁移。BDMC 在 24 和 48 小时处理时通过 Transwell 室试验抑制细胞迁移和侵袭。BDMC 显著降低与 PI3K/Akt、Ras/MEK/ERK 途径相关的蛋白水平,并导致 NF-κB、MMP-2、MMP-9 和 N-钙粘蛋白的表达减少,从而抑制细胞迁移和侵袭。这些发现表明,BDMC 可能是未来抗人 GBM 细胞转移的潜在候选药物。

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