Propofol suppresses proliferation and metastasis of colorectal cancer cells by regulating miR-124-3p.1/AKT3
Propofol suppresses proliferation and metastasis of colorectal cancer cells by regulating miR-124-3p.1/AKT3
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DOI：
10.1007/s10529-019-02787-y
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发表时间：
2020-03-01
影响因子：
2.7
通讯作者：
Xiao, Gaopeng
中科院分区：
文献类型：
--
作者：
Li, Yujin;Dong, Wangjun;Xiao, Gaopeng
研究背景丙泊酚是一种广泛应用于肿瘤切除术的静脉麻醉药，已被证实对包括结直肠癌在内的多种肿瘤具有抗肿瘤作用。虽然丙泊酚在CRC中的作用已有报道，但其作用机制仍知之甚少。本研究进一步探讨丙泊酚对结直肠癌细胞的生物学作用及其机制。方法采用四甲基偶氮唑蓝（MTT）比色法、创伤愈合实验和transwell实验检测细胞增殖、迁移和侵袭能力。通过实时定量聚合酶链反应分析microRNA-124-3p.1（miR-124-3p.1）和AKT丝氨酸/苏氨酸激酶3（AKT 3）的表达水平。Western blot法检测MMP-9、Vimentin和Cyclin D1蛋白的表达。通过TargetScan预测miR-124-3p.1与AKT 3之间的相互作用，并通过双荧光素酶报告基因测定证实。结果异丙酚抑制结直肠癌细胞的增殖、迁移和侵袭。miR-124-3p.1或AKT 3上调的敲低逆转了丙泊酚对CRC细胞增殖和转移的抑制作用。此外，AKT 3是miR-124-3p.1的直接靶点，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。结论丙泊酚通过上调miR-124- 3 p. 1和下调AKT 3抑制结直肠癌细胞增殖、迁移和侵袭，为丙泊酚治疗结直肠癌提供了新的思路。
Background 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. Methods 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. Results 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. Conclusion 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.