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[NB4 cell apoptosis induced by bortezomib combined with As(2)O(3) and its mechanism].
Chen, Xiao-Wen; Xia, Hai-Long; Xia, Rui-Xiang.
Afiliação
  • Chen XW; Department of Hematology, Anhui Medical University First Affiliated Hospital, Hefei 230022, Anhui Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(2): 348-52, 2011 Apr.
Article em Zh | MEDLINE | ID: mdl-21518486
This study was aimed to investigate the apoptosis induced by bortezomib combined with As(2)O(3) in APL cell line NB4 and its mechanism. The apoptotic cells were detected by flow cytometry with Annexin V/propidium iodide double staining; the morphology of apoptotic cells was observed by Hoechst staining, Western blot was used to measure activation of caspase-3 and -9 as well as expression of NOXA; the siRNA technique was used to specifically silence NOXA gene; the lipofectamine 2000 was used to transfect pEGFP-Noxa plasmid and pEGFP vacant vector. The results showed that the bortezomib combined with As(2)O(3) could induce significant apoptosis of NB4 cells and activation of caspase 3 and caspase 9, but As(2)O(3) (0.5 µmol/L) alone could not cause marked activation of caspase cascade and apoptosis of NB4 cells. The expression level of NOXA in NB4 cells induced by bortezomib combined with As(2)O(3) was up-regulated; the activation level of caspase-3 and apoptotic rate of NB4 cells treated by bortezomib combined with As(2)O(3) decreased after specifically silencing the NOXA gene. The high expression of NOXA induced by transfection of plasmid could enhance the caspase 3 activity induced by As(2)O(3) alone. It is concluded that bortezomib can enhance sensitivity of NB4 cells to apoptosis induced by As(2)O(3) which may be related with up-regulation of proapoptotic protein NOXA.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Óxidos / Arsenicais / Pirazinas / Ácidos Borônicos / Apoptose Limite: Humans Idioma: Zh Revista: Zhongguo Shi Yan Xue Ye Xue Za Zhi Assunto da revista: HEMATOLOGIA Ano de publicação: 2011 Tipo de documento: Article País de afiliação: China País de publicação: China
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Óxidos / Arsenicais / Pirazinas / Ácidos Borônicos / Apoptose Limite: Humans Idioma: Zh Revista: Zhongguo Shi Yan Xue Ye Xue Za Zhi Assunto da revista: HEMATOLOGIA Ano de publicação: 2011 Tipo de documento: Article País de afiliação: China País de publicação: China