title: Zoledronic acid suppresses metastasis of esophageal squamous cell carcinoma cells through upregulating the tight junction protein occludin.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Shantou Central Hospital, Shantou, 515041, China.
authors.forename: Canfeng
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Clinical Pharmacy, Shantou Central Hospital, Shantou, 515041, China.
authors.forename: Shubo
authors.initials: S
authors.lastname: Xin
authors.affiliation: Medical College, Hubei University of Arts and Science, Xiangyang, 441053, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Radiation Oncology, The Second People's Hospital of Neijiang City, Neijiang, 641000, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Shantou Central Hospital, Shantou, 515041, China.
authors.forename: Lianxing
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, Luohe Medical College, 148 Daxue-Road, Luohe, 462002, China. youyanjie@163.com.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: You
keywords: Cancer metastasis; Chemotherapy; ESCC; Occludin; Zoledronic acid