Abstract
Diphyllin is a natural component of traditional Chinese medicine, which effectively inhibits V-ATPase activity and affects the progression of cancer. However, few studies have been conducted on esophageal cancer, and the mechanisms remain to be elucidated. The present study revealedthat diphyllin inhibited proliferation and induced S arrest in esophageal cancer cell lines TE-1 and ECA-109. Further experiments revealed that diphyllin inhibited V-ATPase activity and decreased the mRNA expression of mammalian target of rapamycin complex 1 (mTORC1), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF). The present study also revealed that diphyllin inhibited proliferation and reduced the formation of new blood vessels. Diphyllin inhibited blood metastasis by regulating the mTORC1/HIF-1α-/VEGF pathway, therefore it could be considered as a new V-ATPase inhibitor to treat esophageal cancer.
MeSH terms
-
Apoptosis / drug effects
-
Benzodioxoles / pharmacology*
-
Biomarkers, Tumor / metabolism*
-
Carcinoma, Squamous Cell / drug therapy
-
Carcinoma, Squamous Cell / enzymology
-
Carcinoma, Squamous Cell / pathology*
-
Cell Cycle / drug effects
-
Cell Movement / drug effects
-
Cell Proliferation / drug effects
-
Cells, Cultured
-
Esophageal Neoplasms / drug therapy
-
Esophageal Neoplasms / enzymology
-
Esophageal Neoplasms / pathology*
-
Human Umbilical Vein Endothelial Cells / cytology
-
Human Umbilical Vein Endothelial Cells / drug effects
-
Human Umbilical Vein Endothelial Cells / metabolism
-
Humans
-
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
-
Lignans / pharmacology*
-
Mechanistic Target of Rapamycin Complex 1 / metabolism
-
Signal Transduction / drug effects
-
Vacuolar Proton-Translocating ATPases / antagonists & inhibitors*
-
Vascular Endothelial Growth Factor A / metabolism
Substances
-
Benzodioxoles
-
Biomarkers, Tumor
-
HIF1A protein, human
-
Hypoxia-Inducible Factor 1, alpha Subunit
-
Lignans
-
VEGFA protein, human
-
Vascular Endothelial Growth Factor A
-
Mechanistic Target of Rapamycin Complex 1
-
Vacuolar Proton-Translocating ATPases
-
diphyllin