Ni Y-J, Lu J, Zhou H-M
Department of Anesthesiology, The Second Affiliated Hospital of Jiaxing College, Zhejiang, Jiaxing, China.
Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8606-8615. doi: 10.26355/eurrev_201910_19177.
Propofol (2,6-diisopropylphenol) is a commonly used intravenous anesthetic agent. Previous studies suggested that propofol might act as anti-tumor drug in various cancers, including gastric cancer. However, the underlying mechanism is still largely unknown.
1, 5, 10 and 20 μg/ml of propofol were used to treat gastric cancer cell MKN45 for 24, 48 or 72 hours. MTT assay was used to detect the proliferation. Transwell assay was employed to measure the invasion and migration with or without matrigel. The expression of miR-29a, 29b and 29c was assessed by quantitative real time polymerase chain reaction (qRT-PCR). Luciferase assay was introduced to confirm the relationship between miR-29 family member and MMP-2. Western blot was adopted to measure the expression of MMP-2 protein.
The proliferation, migration and invasion of gastric cancer cell MKN45 were gradually decreased after propofol treatment in time- and dose- dependent manners. MiR-29a, b and c were downregulated in MKN45 cells compared with normal gastric mucosa epithelial cell GES-1 and upregulated by propofol. Inhibition of miR-29a, b or c promoted cell proliferation, migration and invasion of MKN45 cells under propofol treatment. MMP-2 was a target and regulated by miR-29 family and propofol. MMP-2 silencing reversed the stimulative effects of miR-29 inhibitor.
Propofol inhibited cell proliferation, migration and invasion by upregulating miR-29a, miR-29b and miR-29c and downregulating MMP-2.
丙泊酚（2,6-二异丙基苯酚）是一种常用的静脉麻醉剂。先前的研究表明，丙泊酚可能在包括胃癌在内的多种癌症中作为抗肿瘤药物发挥作用。然而，其潜在机制仍 largely 未知。
使用 1、5、10 和 20 μg/ml 的丙泊酚处理胃癌细胞 MKN45 24、48 或 72 小时。采用 MTT 法检测增殖情况。使用 Transwell 法在有或无基质胶的情况下测量侵袭和迁移能力。通过定量实时聚合酶链反应（qRT-PCR）评估 miR-29a、29b 和 29c 的表达。引入荧光素酶测定法以确认 miR-29 家族成员与 MMP-2 之间的关系。采用蛋白质免疫印迹法测量 MMP-2 蛋白的表达。
丙泊酚处理后，胃癌细胞 MKN45 的增殖、迁移和侵袭能力呈时间和剂量依赖性逐渐降低。与正常胃黏膜上皮细胞 GES-1 相比，MKN45 细胞中 miR-29a、b 和 c 表达下调，丙泊酚可使其上调。在丙泊酚处理下，抑制 miR-29a、b 或 c 可促进 MKN45 细胞的增殖、迁移和侵袭。MMP-2 是 miR-29 家族和丙泊酚的靶标并受其调控。MMP-2 沉默可逆转 miR-29 抑制剂的刺激作用。
丙泊酚通过上调 miR-29a、miR-29b 和 miR-29c 以及下调 MMP-2 来抑制细胞增殖、迁移和侵袭。
