Wee1 Inhibitor AZD1775 Combined with Cisplatin Potentiates Anticancer Activity against Gastric Cancer by Increasing DNA Damage and Cell Apoptosis.

Based on the mechanisms by which Wee1 inhibitor and cisplatin played their own role, a promising strategy of Wee1 inhibitor combined with cisplatin was proposed, which was investigated in gastric cancer (GC). Either Wee1 inhibitor AZD1775 or cisplatin alone had a certain inhibitory effect on in vitr...

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Publicado en:BioMed Research International Vol. 2018; pp. 1 - 11
Autores principales: Chen, Dongshao, Lin, Xiaoting, Gao, Jing, Shen, Lin, Li, Zhongwu, Dong, Bin, Zhang, Cheng, Zhang, Xiaotian
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 6/7/2018
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 6/7/2018
      vid: 2018
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2018/5813292
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        atl: Wee1 Inhibitor AZD1775 Combined with Cisplatin Potentiates Anticancer Activity against Gastric Cancer by Increasing DNA Damage and Cell Apoptosis.
      aug:
        au:
          Chen, Dongshao
          Lin, Xiaoting
          Gao, Jing
          Shen, Lin
          Li, Zhongwu
          Dong, Bin
          Zhang, Cheng
          Zhang, Xiaotian
        affil: Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing 100142, China
      sug:
        subj:
          Cisplatin Pharmacodynamics
          Tyrosine Kinase Inhibitors Pharmacodynamics
          Drug Combinations
          Cell Line, Tumor Drug Effects
          Stomach Neoplasms
          DNA Drug Effects
          Apoptosis Drug Effects
          DNA Damage
          Human
          In Vitro Studies
          Cell Proliferation Drug Effects
          In Vivo Studies
          Histones Drug Effects
          Biochemical Phenomena Drug Effects
          Cell Movement Drug Effects
      ab: Based on the mechanisms by which Wee1 inhibitor and cisplatin played their own role, a promising strategy of Wee1 inhibitor combined with cisplatin was proposed, which was investigated in gastric cancer (GC). Either Wee1 inhibitor AZD1775 or cisplatin alone had a certain inhibitory effect on in vitro cell proliferation; however, the inhibitory effect was more significant when AZD1775 combined with cisplatin in vitro and in vivo. The underlying mechanisms unveiled that the increased DNA damage indicated by increased γH2AX protein, as well as augmented cell apoptosis indicated by upregulated proapoptotic proteins, was responsible for the significant inhibitory effect of AZD1775 plus cisplatin. Moreover, compared to any single drug, in vitro cell migration and invasion abilities were further attenuated by AZD1775 combined with cisplatin. There were suggestive results that the potentiated cytotoxicity between AZD1775 and cisplatin deserved a deep exploration in the future.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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