Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550003, China.
Pharmacol Rep. 2020 Apr;72(2):418-426. doi: 10.1007/s43440-019-00015-y. Epub 2019 Dec 20.
Anesthesia is a major component of surgery and recently considered an important regulator of cell phenotypes. Here we aimed to investigate propofol, an anesthesia drug, in suppressing pancreatic cancer (PDAC), focusing on A disintegrin and metalloprotease 8, (ADAM8) as a molecular mediator.
Quantitative real-time PCR and western blot were used to assess the change of ADAM8 expression in Panc1 PDAC cells treated with 5 or 10 μg/mL propofol, using cells treated with BB-94 inhibitor as controls. ADAM8 activity was measured through quantifying fluorescence release induced by PEPDAB013 decomposition. MTT assay, scratch wound assay and Matrigel invasion assay were used to investigate the proliferation, migration and invasion of the cells. Western blot and immunohistochemical analysis were used to quantify integrin β1, ERK1/2, MMP2 and MMP9 expression.
Propofol and BB-94 reduced ADAM8 expression, cell proliferation and migration of Panc1 cells. Tumor growth was inhibited by propofol and BB-94, concomitant with downregulation of integrin β1, ERK1/2, MMP2 and MMP9. ADAM8 is downregulated by propofol, leading to inhibition of pancreatic cancer proliferation and migration.
Pancreatic tumor growth is also inhibited by propofol and BB-94, which is attributed to suppression of ERK/MMPs signaling.
麻醉是手术的主要组成部分，最近被认为是细胞表型的重要调节剂。在这里，我们旨在研究麻醉药物丙泊酚在抑制胰腺导管腺癌（PDAC）中的作用，重点研究解整合素金属蛋白酶 8（ADAM8）作为一种分子介质。
使用定量实时 PCR 和 Western blot 检测用 5 或 10μg/mL 丙泊酚处理的 Panc1 PDAC 细胞中 ADAM8 表达的变化，用 BB-94 抑制剂处理的细胞作为对照。通过测量 PEPDAB013 分解诱导的荧光释放来测量 ADAM8 活性。MTT 测定、划痕伤口测定和 Matrigel 侵袭测定用于研究细胞的增殖、迁移和侵袭。Western blot 和免疫组织化学分析用于定量整合素 β1、ERK1/2、MMP2 和 MMP9 的表达。
丙泊酚和 BB-94 降低了 Panc1 细胞中 ADAM8 的表达、细胞增殖和迁移。丙泊酚和 BB-94 抑制肿瘤生长，同时下调整合素 β1、ERK1/2、MMP2 和 MMP9。丙泊酚下调 ADAM8，从而抑制胰腺癌细胞的增殖和迁移。
丙泊酚和 BB-94 也抑制胰腺肿瘤的生长，这归因于 ERK/MMPs 信号的抑制。
