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异丙酚可预防白细胞介素-13 诱导的人结直肠癌细胞上皮-间充质转化。

Propofol prevents IL-13-induced epithelial-mesenchymal transition in human colorectal cancer cells.

机构信息

Department of Anaesthesiology, Tongren Hospital, Shanghai JiaoTong University School of Medicine, 1111 Xian Xia Road, Shanghai 200336, China.

出版信息

Cell Biol Int. 2018 Aug;42(8):985-993. doi: 10.1002/cbin.10964. Epub 2018 Apr 16.

DOI:10.1002/cbin.10964
PMID:29569786
Abstract

Accumulating evidence showed that cytokines are involved in the development of cancer. IL-13 was showed to induce epithelial-mesenchymal transition and promote metastasis in colorectal cancer, providing a promising therapeutic target for cancer patients. Interestingly, recent studies showed that propofol, one of most common intravenous anesthetic agent, may have antitumor function in different cancer type. However, the impact of propofol on colorectal cancer and IL-13 induced epithelial-mesenchymal transition remains unknown. Herein, we found that propofol can effectively suppress cell proliferation in colorectal cell lines RKO and SW480 cells by using MTT assay. Furthermore, wound healing assay and migration assay demonstrated that propofol has the ability to inhibit epithelial-mesenchymal transition that induced by IL-13 in RKO and SW480 cells. Mechanistically, we found propofol treatment causes up-regulation of miR-361 and miR-135b, that suppress expression of STAT6 and thereafter leads to the inhibition of IL-13/STAT6/ZEB1 signaling pathway. In conclusion, our data for the first time demonstrated that propofol may serve as a novel therapeutic drug for targeting IL-13. The aggressive function of IL-13/STAT6/ZEB1 axis in colorectal cancer was impaired by propofol through miR-361 and miR-135b.

摘要

越来越多的证据表明细胞因子参与了癌症的发展。IL-13 被证明可诱导结直肠癌细胞发生上皮-间质转化并促进转移,为癌症患者提供了一个有前途的治疗靶点。有趣的是,最近的研究表明,异丙酚是最常用的静脉麻醉剂之一,可能对不同类型的癌症具有抗肿瘤作用。然而,异丙酚对结直肠癌和 IL-13 诱导的上皮-间质转化的影响尚不清楚。在此,我们通过 MTT 检测发现异丙酚可有效抑制结直肠细胞系 RKO 和 SW480 细胞的增殖。此外,划痕愈合实验和迁移实验表明,异丙酚具有抑制 IL-13 诱导的 RKO 和 SW480 细胞上皮-间质转化的能力。在机制上,我们发现异丙酚处理导致 miR-361 和 miR-135b 的上调,抑制 STAT6 的表达,从而抑制 IL-13/STAT6/ZEB1 信号通路。总之,我们的数据首次表明,异丙酚可能作为一种针对 IL-13 的新型治疗药物。异丙酚通过 miR-361 和 miR-135b 抑制结直肠癌细胞中 IL-13/STAT6/ZEB1 轴的侵袭功能。

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