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

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 1 alpha (HIF-1 alpha), 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-1 alpha 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-1 alpha/VEGF pathway.

Automated summary

The study aimed to investigate the mechanism by which arsenic sulfide (As4S4) represses the metastasis of hepatocellular carcinoma (HCC). Cell viability, migration, invasion, and angiogenesis were assessed to evaluate the effect of As4S4 on HCC cell lines. Key molecules involved in metastasis were examined to determine the underlying pathway. The results showed that As4S4 effectively suppressed the proliferation, migration, invasion, and angiogenesis of HCC cells, and it achieved this by inhibiting the expression of HIF-1 alpha/VEGF pathway-related molecules.