Department of Anesthesiology, The First People's Hospital of Yunnan Province, Jin Bi Road, Xishan District, Kunming, 650000, Yunnan, China.
Department of Anesthesiology, Yongping County People's Hospital, Dali, 672600, Yunnan, China.
Biotechnol Lett. 2020 Mar;42(3):493-504. doi: 10.1007/s10529-019-02787-y. Epub 2020 Jan 1.
Propofol, an extensively used intravenous anesthetic agents during cancer resection surgery, has been confirmed to execute anti-tumor effect on multiple cancers, including colorectal cancer (CRC). Although the role of propofol in CRC has been previously reported, its action mechanism remains poorly understood. This study further explored the biological function and underlying mechanism of propofol in CRC cells.
The cell proliferation, migration and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, wound healing assay and transwell assay, respectively. The expression levels microRNA-124-3p.1 (miR-124-3p.1) and AKT serine/threonine kinase 3 (AKT3) was analyzed by quantitative real-time polymerase chain reaction. Western blot assay was employed to measure the protein expression of MMP-9, Vimentin and Cyclin D1. The interaction between miR-124-3p.1 and AKT3 was predicted by TargetScan and confirmed by dual-luciferase reporter assay.
Propofol inhibited CRC cell proliferation, migration and invasion. Knockdown of miR-124-3p.1 or AKT3 upregulation reversed the inhibitory effects of propofol on CRC cell proliferation and metastasis. Besides, AKT3 was a direct target of miR-124-3p.1 and its overexpression abated the anti-tumor effect of miR-124-3p.1 on CRC cell proliferation and metastasis.
Propofol inhibited CRC cell proliferation, migration and invasion by upregulating miR-124-3p.1 and downregulating AKT3, providing a new sight for propofol treatment of CRC.
丙泊酚是一种广泛应用于癌症切除术的静脉麻醉剂，已被证实对多种癌症具有抗肿瘤作用，包括结直肠癌（CRC）。尽管丙泊酚在 CRC 中的作用已被先前报道，但它的作用机制仍不清楚。本研究进一步探讨了丙泊酚在 CRC 细胞中的生物学功能和潜在机制。
通过噻唑蓝（MTT）法、划痕愈合试验和 Transwell 试验分别评估细胞增殖、迁移和侵袭。通过定量实时聚合酶链反应分析 microRNA-124-3p.1（miR-124-3p.1）和丝氨酸/苏氨酸激酶 3（AKT3）的表达水平。采用 Western blot 试验测量 MMP-9、波形蛋白和细胞周期蛋白 D1 的蛋白表达。通过 TargetScan 预测 miR-124-3p.1 与 AKT3 之间的相互作用，并通过双荧光素酶报告基因试验进行验证。
丙泊酚抑制 CRC 细胞增殖、迁移和侵袭。下调 miR-124-3p.1 或上调 AKT3 逆转了丙泊酚对 CRC 细胞增殖和转移的抑制作用。此外，AKT3 是 miR-124-3p.1 的直接靶标，其过表达减弱了 miR-124-3p.1 对 CRC 细胞增殖和转移的抗肿瘤作用。
丙泊酚通过上调 miR-124-3p.1 和下调 AKT3 抑制 CRC 细胞增殖、迁移和侵袭，为丙泊酚治疗 CRC 提供了新的思路。
