title: Inhibition of cyclin D1 enhances sensitivity to radiotherapy and reverses epithelial to mesenchymal transition for esophageal cancer cells.
abstract: Acquired radioresistance during radiotherapy has significantly affected the treatment efficacy in esophageal cancer. Many of radioresistant cancer cells demonstrated epithelial-mesenchymal transition (EMT).We found in previous study that a radioresistant cell line (KYSE-150R) possessed EMT characteristic with cyclin D1 overexpression. Cyclin D1 has been demonstrated to affect the radiation sensitivity in cancer cells. To elucidate the molecular functions of cyclin D1 on EMT phenotypes and esophageal cancer radiosensitivity, we treated the radioresistant esophageal cancer cells (KYSE-150R) and parental cells (KYSE-150) with cyclin D1 small interfering RNA (siRNA). The cell proliferation rate of KYSE-150R and the radiation survival fraction were significantly decreased in cyclin D1 siRNA treatment group. Knocking down cyclin D1 resulted in G0/G1 arrest in KYSE-150R cells. The average number of irradiation-induced γ-H2AX foci increased in the cells treated with cyclin D1 siRNA, indicating impaired DNA double-strand break (DSB) repair in KYSE-150R cells. Cyclin D1 also reversed EMT phenotypes with significantly increased expression of E-cadherin in KYSE-150R cells. However, cyclin D1 siRNA have no radiosensitizing effects on KYSE-150 cells, with no obvious change in EMT marker expression .Our work showed that EMT phenotypes can be reduced and the radiosensitivity of esophageal cancer cells can be enhanced by inhibiting cyclin D1.
authors.affiliation: Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Huafang
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Xiance
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Lanxiao
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Fei
authors.affiliation: Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China.
authors.forename: Xuebang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, China. wzxiecongying@163.com.
authors.forename: Congying
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. billy07@wzhospital.cn.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Chen
mesh_terms: D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000528:radiation effects; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage
chemical_list: D015820:Cadherins; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; D019938:Cyclin D1
keywords: Cyclin D1; Epithelial-mesenchymal transition; Esophageal cancer; Radioresistance