Background: Angiotensin II (Ang II) and its receptor, Angiotensin II receptor type 1 (AGTR1), have been implicated in the proliferation of cancer cells across various tumor types. This study aims to examine the impact of Ang II and AGTR1 on esophageal squamous cell carcinoma (ESCC) cells.

Methods: The clonogenicity and proliferation of tumor cells were evaluated through Clone Formation and Cell Counting Kit-8 (CCK-8) assays. Cell migration and invasion were determined utilizing Transwell assays. Flow cytometry was employed to analyze the cell cycle. Additionally, to investigate the expressions of genes associated with cell growth, migration, infiltration, and Janus kinase-signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathways, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were utilized.

Results: In the current study, it was observed that increasing the concentration of Ang II significantly augmented the proliferation of ESCC cells. However, with the addition of its inhibitor losartan, the proliferative activity of ESCC cells was significantly reduced with the increase of losartan concentration (p < 0.05). The inhibition of AGTR1 also markedly reduced the proliferative activity of ESCC cells, counteracting the effect induced by Ang II treatment (p < 0.05). Additionally, Ang II was found to stimulate the migration and invasion of ESCC cells, facilitate the transition of these cells from the first gap (G1) to the synthesis (S) phase, and impede apoptosis (p < 0.05). However, treatment with losartan and AGTR1 inhibition significantly diminished the number of migratory and invasive cells, inhibited the transition from G1 to S phase, and promoted apoptosis in ESCC cells (p < 0.05). Regarding the mechanism, our research team found that Ang II and AGTR1 can enhance the proliferation and invasion of ESCC cells and inhibit their apoptosis via the JAK/STAT3 signaling pathway. Nevertheless, the AGTR1 blocker, losartan, effectively obstructed this process.

Conclusion: The activation of the JAK/STAT3 signaling pathway by Ang II and AGTR1 promotes the advancement of ESCC tumors. Consequently, targeting Ang II and AGTR1 could potentially emerge as a promising strategy for ESCC treatment.