Shan Huang

Publications (2)3.41 Total impact

• Source

  Available from: PubMed Central

  Article: Inhibition of mitotic kinase Aurora suppresses Akt-1 activation and induces apoptotic cell death in all-trans retinoid acid-resistant acute promyelocytic leukemia cells.

  Duo-Rong Xu, Shan Huang, Zi-Jie Long, Jia-Jie Chen, Zheng-Zhi Zou, Juan Li, Dong-Jun Lin, Quentin Liu
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  ABSTRACT: Aurora kinase ensures accurate chromosome segregation during cell cycle, maintaining genetic integrity in cell division. VX-680, a small-molecule Aurora kinase inhibitor, interferes with mitotic entry and formation of bipolar spindles. Here, we evaluated VX-680 as a potential agent for treatment of all-trans retinoid acid (ATRA)-resistant acute promyelocytic leukemia (APL) in vitro. CD11b expression was utilized to assess cell differentiation by flow cytometry. Immunofluorescence staining was conducted to analyze formation of cell monopolar spindle. Cell proliferation was evaluated by MTT assay. Sub-G1 population and Annexin V/PI staining were used to measure cell apoptosis. Hoechst 33342 staining was applied for identifying morphological changes in nucleus of apoptotic cell. Aurora-A (Aur-A) activation and the signaling pathways involved in apoptosis were detected by Western blot. JC-1 probe was employed to measure mitochondrial depolarization. VX-680 inhibited Aur-A by reducing autophosphorylation at the activation site, Thr288, accompanied by producing monopolar mitotic spindles in APL cell line NB4-R2 that was resistant to ATRA. In addition, we found that VX-680 inhibited cell proliferation as assessed by MTT assay. Flow cytometry showed that VX-680 led to apoptotic cell death in both dose- and time-dependent manners by either Sub-G1 or Annexin V/PI analysis. Hoechst 33342 staining represented typical apoptotic cells with nuclear fragmentation in VX-680 treated cells. Importantly, VX-680 inhibition of Aurora kinase suppressed Akt-1 activation and induced mitochondrial depolarization, which eventually resulted in apoptosis by activation of caspase pathway, as indicated by increasing proteolytic cleavage of procaspase-3 and poly ADP ribose polymerase (PARP) in NB4-R2 cells. Our study suggested potential clinical use of mitotic Aurora kinase inhibitor in targeting ATRA-resistant leukemic cells.
  Journal of Translational Medicine 01/2011; 9:74. · 3.41 Impact Factor
• Article: [Significance of sRANKL/OPG ratio in diagnosis of multiple myeloma bone disease].

  Duo-Rong Xu, Chang Su, Wai-Yi Zou, Hui-Ru Xu, Shan Huang, Juan Li, Shao-Kai Luo
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  ABSTRACT: This study was purposed to investigate the relationship between the levels of soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) in serum of the patients with multiple myeloma (MM) and multiple myeloma bone disease (MBD). The serum levels of sRANKL, OPG, tartrate-resistant acid phosphatase-5b (TRAP-5b) and C-terminal telopeptide of collagen I (CTP-I) which both are indexes for metabolism of osteoclast (OC) in newly diagnosed MM patients (n=42, experimental group) and healthy persons (n=25, control group) were detected by enzyme-linked immunosorbent assay. The roentgenography was used to determine bone damage in MM patients at the same time. According to these results acquired, the correlation of sRANKL/OPG ratio with levels of TRAP-5b/CTP-I, the incidence and degree of bone destruction were analyzed. The results indicated that the level of sRANKL (median value 9.33 microg/L) increased and level of OPG (median value 4.93 microg/L) decreased and the sRANKL/OPG ratio (2.65) increased significantly in experimental group. Compared with control group, the differences in all the corresponding indicators were statistically significant (p<0.05). The sRANKL/OPG ratio was closely related to levels of TRAP-5b (r=0.512, p<0.05) and CTP-I (r=0.481, p<0.05) in MM patients. After all patients in experimental groups were divided into group with bone destruction (n=29) and without bone destruction (n=13), the sRANKL/OPG ratio in the group with bone destruction was 5.13 and much higher than that in group without bone destruction (1.12) (p<0.05). A close correlation between the sRANKL/OPG ratio and degree of bone destruction (r=0.445, p<0.05) was acquired when all MM patients were divided into three groups according to degree of bone destruction, but no difference between the ratio and clinical classification and International Staging System (ISS) in MM patients was found. It is concluded that the sRANKL/OPG ratio in serum of MM patients is significantly elevated, which may be closely related to increase metabolism of OC along with the incidence and degree of bone destruction. In short, the sRANKL/OPG ratio can be used as a reference index for the diagnosis of MBD.
  Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 04/2010; 18(2):376-80.