title: Wogonin as a targeted therapeutic agent for EBV (+) lymphoma cells involved in LMP1/NF-κB/miR-155/PU.1 pathway.
abstract: Wogonin is an encouraging choice for clinical use owing to its potent anti-tumor and anti-inflammatory effects with the high safety profile. However, wogonin for targeted therapy of lymphoma was not well addressed. In this study, we focused on its anticancer effect alongside with the underlying mechanisms for targeted therapy in EBV-positive lymphoma. This will facilitate its introduction to clinical use, which is planned in the near future.
  
  
  
  Cell proliferation was studied by CCK8. Flow cytometry was used to analyze the apoptosis and the cycle arrest of cells. Further, we also used immunofluorescent staining to detect the morphologic changes of the apoptotic cells. The expression of LMP1/miR-155/p65/pp65/PU.1 was evaluated by quantitative real-time PCR (qRT-PCR) and western blot, while that of NF-κB was analyzed by EMSA. At last, immunohistochemical staining was applied to assess the expression of target proteins and relevant molecules.
  
  
  
  In vitro, wogonin induced the apoptosis of Raji cells by downregulating the expression of NF-κB through LMP1/miR-155/NF-κB/PU.1 pathway, which was in a dose and time-dependent manner. In vivo, wogonin could suppress tumor growth, associated with the downregulation of ki67, p65 and upregulation of PU.1.
  
  
  
  Wogonin could suppress tumor growth and induce cell apoptosis by inhibiting the expression of NF-κB. Taken these findings, we concluded that wogonin could be a potential targeted therapeutic agent for EBV-positive lymphoma with the expression of LMP1 through the pathway of LMP1/NF-κB/miR-155/PU.1.
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, the Affiliated Zhongda Hospital, Southeast University, Nanjing, 210009, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, the Affiliated Zhongda Hospital, Southeast University, Nanjing, 210009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, the Affiliated Zhongda Hospital, Southeast University, Nanjing, 210009, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Medical School, The Second Hospital of Nanjing Affiliated to Southeast University, Nanjing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, the Affiliated Zhongda Hospital, Southeast University, Nanjing, 210009, China.
authors.forename: Jumah Masoud Mohammad
authors.initials: JM
authors.lastname: Salmani
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, the Affiliated Zhongda Hospital, Southeast University, Nanjing, 210009, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, the Affiliated Zhongda Hospital, Southeast University, Nanjing, 210009, China.
authors.forename: Zhewei
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Medical School, the Affiliated Zhongda Hospital, Southeast University, Nanjing, 210009, China. cba8888@hotmail.com.
authors.forename: Baoan
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy*; D044950:Flavanones / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000821:virology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000235:genetics; D014763:Viral Matrix Proteins / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D035683:MicroRNAs; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014763:Viral Matrix Proteins; D000099232:Proto-Oncogene Protein Spi-1; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C524942:MIRN155 microRNA, human; C085514:wogonin
keywords: Apoptosis; EBV infection; Lymphoma; NF-κB; Wogonin