ET-1 promotes the growth and metastasis of esophageal squamous cell carcinoma via activating PI3K/Akt pathway

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide. Previous studies confirmed that endothelin-1 (ET-1) serves as an oncogene and therapeutic target in various tumors. However, the role and mechanism of ET-1 in the progression of ESCC remains largely unclear. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA level of ET-1 in ESCC tissues and cell lines. Cell counting kit-8 (CCK-8), flow cytometry and Transwell assay were performed to examine the proliferation, cell cycle arrest, invasion and migration capacity of ESCC cells. Western blot was applied to measure the expression of ET-1 and PI3K/Akt pathway-related proteins. Furthermore, we also assessed the effect of ET-1 on tumor growth in vivo. RESULTS: ET-1 was highly expressed in ESCC tissues and associated with poor outcomes. Knockdown of ET-1 significantly inhibited the proliferation, migration and invasion capacity of ESCC cells and promoted cell cycle arrest. Mechanistically, silencing of ET-1 exerts anti-proliferation and anti-metastasis activities via inactivation of the PI3K/Akt signaling pathway in ESCC in vitro and in vivo. CONCLUSIONS: These findings uncover the effective suppression of cell proliferation and metastasis through silencing of ET-1 and blocking the PI3K/Akt signaling pathway, which is an attractive therapeutic regimen for the treatment of ESCC.