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丙泊酚通过下调 ERK/VEGF 信号通路抑制 NET1 表达抑制肝癌。

Propofol suppresses hepatocellular carcinoma by inhibiting NET1 through downregulating ERK/VEGF signaling pathway.

机构信息

Department of Anaesthesiology, Shanghai Xuhui Central Hospital, Shanghai, 200031, China.

Department of Anaesthesiology, Eastern Hepatobiliary Surgical Hospital, Shanghai, 200438, China.

出版信息

Sci Rep. 2020 Jul 8;10(1):11208. doi: 10.1038/s41598-020-67693-0.

Abstract

Hepatocellular carcinoma (HCC) is the leading cause of tumor death in China with high mortality since its strong metastatic potential. Currently, treatment against advanced HCC is poorly efficient and thus screening new drugs to prevent the HCC invasion is of great significance to improve the survival rate of patients with HCC. From the results of this study, we concluded that propofol, a widely used anesthetics could prevent the proliferation by MTT assay. The scratch wound and invasion assays showed that migratory property and invasiveness in HCC cells SMMC-7721 was inhibited by propofol. This process was probably mediated by NET1 since NET1 overexpression offset the repressive effect of propofol on the invasiveness and migratory ability of SMMC-7721 cells. Furthermore, propofol treatment also reduced p-ERK1/2 and VEGF level by western blot analysis. Similar observation was found when NET1 was silenced. Thus, the results of this study provided valuable clinical therapy potential of propofol against liver cancer. We also disclosed molecular mechanism underlying the regulation of invasion and migration in HCC cells by NET1.

摘要

肝细胞癌 (HCC) 是中国肿瘤死亡的主要原因,由于其较强的转移潜能,死亡率很高。目前,针对晚期 HCC 的治疗效果不佳,因此筛选预防 HCC 侵袭的新药对于提高 HCC 患者的生存率具有重要意义。从本研究结果可知,广泛用于麻醉的丙泊酚可通过 MTT 测定法防止增殖。划痕伤口和侵袭试验表明,丙泊酚抑制 HCC 细胞 SMMC-7721 的迁移特性和侵袭性。这一过程可能是由 NET1 介导的,因为 NET1 的过表达抵消了丙泊酚对 SMMC-7721 细胞侵袭和迁移能力的抑制作用。此外,丙泊酚处理还通过 Western blot 分析降低了 p-ERK1/2 和 VEGF 水平。当 NET1 被沉默时也发现了类似的观察结果。因此,本研究结果为丙泊酚在肝癌中的临床治疗提供了有价值的潜在作用。我们还揭示了 NET1 调节 HCC 细胞侵袭和迁移的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cbc/7343826/82a0144cf15c/41598_2020_67693_Fig1_HTML.jpg

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