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Erianin, a natural compound extracted from  Dendrobium chrysotoxum Lindl , has potential therapeutic benefits against various tumors. However, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. Cell proliferation was analyzed by CCK8, colony-formation, and EdU proliferation assays, while cell migration was evaluated through wound healing assays as well as determination of the protein expression levels of epithelial-to-mesenchymal transition (EMT) markers and β-catenin. Apoptosis was measured by flow cytometry. RNA sequencing (RNA-seq) and bioinformatic analyses were performed to elucidate the underlying mechanisms of erianin in ESCC. Enzyme-linked immunosorbent assay (ELISA) was used to determine intracellular cGMP, cleaved-PARP, and caspase-3/7 activity, while mRNA and protein levels were determined by qRT-PCR and western blotting, respectively. Our results indicate that erianin significantly inhibited ESCC cell proliferation and migration while also promoting apoptosis. Mechanistically, RNA sequencing coupled with KEGG enrichment analysis and functional assays revealed that activation of the cGMP-PKG pathway contributed to the antitumor effects of erianin, whereas the c-GMP-dependent protein kinase inhibitor KT5823 significantly attenuated these effects. In conclusion, our results demonstrate that erianin suppresses the proliferation of ESCC cells by activating the cGMP-PKG pathway, suggesting that erianin could be a promising candidate for the treatment of ESCC.

Erianin Exerts Antineoplastic Effects on Esophageal Squamous Cell Carcinoma Cells by Activating the cGMP-PKG Signaling Pathway