title: [Apoptosis-inducing effect of valproic acid combined with arsenic trioxide on RPMI 8226 cells and its mechanism].
abstract: This study was aimed to investigate the apoptosis-inducing effect of valproic acid (VPA) combined with arsenic trioxide (ATO) on human multiple myeloma RPMI 8226 cells and its mechanism. The cell proliferation of RPMI 8226 cells was assayed by CCK-8 method. The cell apoptosis were detected by flow cytometry. Semiquantitative RT-PCR and Western blot were applied respectively to detect the mRNA and protein expression level of BCL-2, BAX, caspase-8 and caspase-9 gene. The results showed that both the VPA and ATO inhibited RPMI 8226 cell proliferation. The combination of ATO and VPA has synergistic effect (Q values greater than 1.15). The RPMI 8226 cell apoptosis rate in combined drug group was significantly higher than that in single drug group (P < 0.05). The mRNA and protein expressions of BCL-2 gene in combined drug group decreased, while the mRNA and protein expressions of BAX, caspase-8 and caspase-9 significantly increased, compared with single drug group (P < 0.05) . It is concluded that VPA can enhance the sensitivity of RPMI 8226 cells to ATO-induced apoptosis, which may be associated with decreasing the BCL-2 expression and increasing the BAX, caspase-8 and caspase-9 gene expression.
authors.affiliation: Department of Hematology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Wang
authors.affiliation: Department of Hematology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China. E-mail:zhangmei@medmail.com.cn.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D001152:Arsenicals; C494826:BAX protein, human; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D014635:Valproic Acid; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D000077237:Arsenic Trioxide