Zoledronic acid suppresses metastasis of esophageal squamous cell carcinoma cells through upregulating the tight junction protein occludin
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We have previously demonstrated the radio-sensitizing effect of zoledronic acid (ZOL), a third generation bisphosphonate, on human esophageal squamous cell carcinoma (ESCC) cells. Here we show that ZOL suppresses metastatic progression of ESCC cells mainly through up-regulating the tight junction protein occludin. Exposure to ZOL at lower concentrations dramatically reduced migration and invasion of ESCC cells. In addition, ZOL treatment decreased the expression of mesenchymal markers, vimentin and N-cadherin, while increased the expression of the tight junction protein occludin. Moreover, ectopic expression of Slug, a well-known transcriptional repressor of occludin, partially but significantly abrogated the effect of ZOL on occludin expression and subsequently rescued the malignant metastatic phenotype, suggesting that Slug is one of the mediators underlying the anti-metastatic effect of ZOL. The present study is the first to report the significance of ZOL on ESCC metastasis. These data are promising for the future application of this drug regimen in patients with ESCC.
KeywordsESCC Chemotherapy Cancer metastasis Zoledronic acid Occludin
We thank Mr. Zhen Zhang (Department of Biochemistry and Molecular Biology, University of Kansas Medical Center) for his careful reading of this manuscript and kind suggestion. This work was supported in part by the Science and Technology Planning Project of Henan Province, China (142102310464), the Key Research Foundation of Higher Education of Henan Province, China (15B320003), the Annual Natural Science Foundation of Luohe Medical College (Y.-J. You, 2015), the Natural Science Foundation of Hubei Province (2014CFC1154), the Foundation of Medical College of Hubei University of Arts and Science (YXKY 201402) and the Scientific Research Foundation for Doctoral Program of Hubei University of Arts and Science (X. Qin).
Conflict of interest
The authors declare no conflicts of interest.
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