硫化砷通过抑制 HIF-1α/VEGF 通路抑制肝癌转移。

Arsenic Sulfide Inhibits Hepatocellular Carcinoma Metastasis by Suppressing the HIF-1α/VEGF Pathway.

机构信息

Department of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 200092 Shanghai, China.

出版信息

Front Biosci (Landmark Ed). 2023 Jul 27;28(7):152. doi: 10.31083/j.fbl2807152.

DOI:10.31083/j.fbl2807152

PMID:37525902

Abstract

BACKGROUND

Metastasis is one of the principal reasons of cancer mortality from hepatocellular carcinoma (HCC). The goal of our investigation was to examine the mechanism by which arsenic sulfide (As4S4) represses the metastasis of HCC.

METHODS

The cell counting kit-8 (CCK-8) assay was conducted to observe cell viability of HCC cell lines HepG2 and Hep3B following As4S4 treatment, and their metastasis was studied using the wound-healing and transwell assays. HCC-induced angiogenesis of human umbilical vein endothelial cells (HUVEC) was assessed by tube formation assay. Enzyme-linked immunosorbent assay (ELISA), western blot, quantitative polymerase chain reaction and immunofluorescence staining were utilized to evaluate key molecules involved in metastasis, including hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), Vimentin, N-cadherin and E-cadherin.

RESULTS

As4S4 suppressed the proliferation, migration and invasion of HepG2 and Hep3B cell lines in a concentration-dependent pattern, and inhibited HCC cell-induced angiogenesis of HUVEC in the tube formation assay. Treatment with As4S4 also decreased the expression of crucial elements involved in the metastasis of HCC cells, including HIF-1α and VEGF, while reducing epithelial-mesenchymal transition, as shown by Western blot, ELISA and immunofluorescence staining.

CONCLUSIONS

Overall, results above indicate that As4S4 suppresses the metastasis of HCC cells via the HIF-1α/VEGF pathway.

摘要

背景

转移是肝癌（HCC）患者死亡的主要原因之一。我们的研究目的是探讨硫化砷（As4S4）抑制 HCC 转移的机制。

方法

用细胞计数试剂盒-8（CCK-8）检测 As4S4 处理后 HepG2 和 Hep3B 肝癌细胞系的细胞活力，并通过划痕愈合和 Transwell 实验研究其转移情况。用管形成实验评估 HCC 诱导的人脐静脉内皮细胞（HUVEC）血管生成。酶联免疫吸附试验（ELISA）、Western blot、实时定量聚合酶链反应和免疫荧光染色用于评估转移相关的关键分子，包括缺氧诱导因子 1α（HIF-1α）、血管内皮生长因子（VEGF）、波形蛋白、N-钙黏蛋白和 E-钙黏蛋白。

结果

As4S4 呈浓度依赖性抑制 HepG2 和 Hep3B 细胞系的增殖、迁移和侵袭，并抑制 HCC 细胞在管形成实验中诱导的 HUVEC 血管生成。As4S4 处理还降低了 HCC 细胞转移过程中关键因子的表达，包括 HIF-1α 和 VEGF，同时通过 Western blot、ELISA 和免疫荧光染色降低上皮-间充质转化。