title: Berberine sensitizes nasopharyngeal carcinoma cells to radiation through inhibition of Sp1 and EMT.
abstract: Nasopharyngeal carcinoma (NPC) is a tumor of epithelial origin with radiotherapy as its standard treatment. However, radioresistance remains a critical issue in the treatment of NPC. This study aimed to investigate the effect of berberine on the proliferation, cell cycle regulation, apoptosis, radioresistance of NPC cells and whether specificity protein 1 (Sp1) is a functional target of berberine. Our results showed that treatment with berberine reduced the proliferation and viability of CNE-2 cells in a dose- and time‑dependent manner. Berberine induced cell cycle arrest in the G0/G1 phase and apoptosis. In CNE-2 cells exposed to gamma‑ray irradiation, berberine reduced cell viability at various concentrations (25, 50, 75 and 100 µmol/l). Berberine significantly decreased mRNA and protein expression of Sp1 in the CNE-2 cells. Mithramycin A, a selective Sp1 inhibitor, enhanced the radiosensitivity and the rate of apoptosis in the CNE-2 cells. Berberine inhibited transforming growth factor-β (TGF-β)-induced tumor invasion and suppressed epithelial-to-mesenchymal transition (EMT) process, as evidenced by increased E-cadherin and decreased vimentin proteins. Sp1 may be required for the TGF-β1-induced invasion and EMT by berberine. In conclusion, berberine demonstrated the ability to suppress proliferation, induce cell cycle arrest and apoptosis, and enhance radiosensitivity of the CNE-2 NPC cells. Sp1 may be a target of berberine which is decreased during the radiosensitization of berberine.
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yu-Tao
authors.initials: YT
authors.lastname: Qin
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Zhu-Xin
authors.initials: ZX
authors.lastname: Wei
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jing-Jian
authors.initials: JJ
authors.lastname: Xiao
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Ren-Sheng
authors.initials: RS
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D001599:Berberine / Q000494:pharmacology*; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D011838:Radiation-Sensitizing Agents; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D001599:Berberine