title: [Mechanisms of cladribine-inducing apoptosis of multiple myeloma RPMI 8226 cells in vitro].
abstract: This study was purposed to explore the mechanisms of cladribine (2-CdA)-inducing apoptosis of multiple mycloma RPMI 8226 cells. The MTT method was used to determine cell proliferation after being treated with 2-CdA. Apoptosis and cell cycle progression were examined by flow cytometry. Transmission electron microscopy was used to observe ultrastructural changes of RPMI 8226 cells. RT-PCR and Western blot were used to analyze the mRNA and protein expression levels of BCL-2, MCL-2 and caspase-3 respectively. The results showed that the 2-CdA inhibited proliferation of RPMI 8226 cells in time and dose-dependent manner. Typical apoptotic morphological and ultrastructure changes could be observed by electron microscopy. Flow cytometry showed that 2-CdA induced myeloma cell apoptosis and arrested myeloma cells in the G2/M phase. The mRNA expression of BCL-2 and MCL-1 decreased but that of caspase-3 not apparently changed. Western blot results suggested that the change trend of BCL-2 MCL-1 and caspase-3 was the same as result of RT-PCR. It is concluded that 2-CdA exhibits inhibitory effects on RPMI 8226 cells in vitro. Activating the mitochondrial and death receptor pathways of apoptosia may be the potential mechanism, meanwhile, the cell cycle arrest may also play a critical role in apoptosis.
authors.affiliation: Department of Hematology, Tangdu Hospital of Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.
authors.forename: Nai-Cen
authors.initials: NC
authors.lastname: Zhou
authors.affiliation: Department of Hematology, The First Hospital, Xi'an Jiaotong University, Xian 710061, Shanxi Province, China.
authors.forename: Mei-Ying
authors.initials: MY
authors.lastname: Qi
authors.affiliation: Department of Hematology, The First Hospital, Xi'an Jiaotong University, Xian 710061, Shanxi Province, China.
authors.forename: Bao-Lan
authors.initials: BL
authors.lastname: Liu
authors.affiliation: Department of Hematology, The First Hospital, Xi'an Jiaotong University, Xian 710061, Shanxi Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Hematology, The First Hospital, Xi'an Jiaotong University, Xian 710061, Shanxi Province, China. E-mail: liuxin59221@medmail.com.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017338:Cladribine / Q000494:pharmacology*; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017338:Cladribine; D053148:Caspase 3