Beta-Elemene Suppresses Metastasis of Human Esophageal Cancer Cell by Downregulating Heat Shock Protein 70/Mothers against Decapentaplegic Homolog 2 Pathway
Department of Oncology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, 1The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou 310000, China
W. J. Chen, The Second Clinical Medical School of Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou 310000, China, E-mail: email@example.com
In this study, we tried to illuminate the role and underlying mechanism of beta-elemene in esophageal squamous cell carcinoma especially the metastasis. 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay was performed to determine the cytotoxicity of beta-elemene and its role in esophageal squamous cell carcinoma cell proliferation. Wound healing assay and transwell assays were used to elucidate the roles of betaelemene on cell migration and invasion abilities of esophageal squamous cell carcinoma cells. Quantitative polymerase chain reaction and western blot assays were carried out to assess the messenger RNA and protein expression under beta-elemene treatment. Immunofluorescence staining was performed to detect the heat shock protein 70 expression regulated by beta-elemene. The heat shock protein 70 ectopic expression plasmid was used to perform the rescue experiments. In this study, we found that beta-elemene significantly inhibited the cell survival and cell proliferation and suppressed cell migration and invasion abilities of esophageal squamous cell carcinoma cell line. Mechanistically, we observed that beta-elemene downregulated heat shock protein 70 expressions and reversed epithelial-mesenchymal transition. Furthermore, the studies also indicated that beta-elemene downregulated the phosphorylation of extracellular regulated kinase, mothers against decapentaplegic homolog 2 and mothers against decapentaplegic homolog 3 expression. In addition, we confirmed that ectopic expression of heat shock protein 70 not only promoted cell migration, epithelialmesenchymal transition and mothers against decapentaplegic homolog 2 phosphorylation in esophageal squamous cell carcinoma cell line cells, but also reversed beta-elemene suppressed cell migration in TE-1 cells. Taken together, all results elucidated that beta-elemene suppresses metastasis of human esophageal squamous cell carcinoma by modulating the expression of heat shock protein 70 and the activation of extracellular regulated kinase and transforming growth factor beta signaling pathways at least partially.