title: [Effects of docetaxel on proliferation and apoptosis of human multiple myeloma cell RPMI8226].
abstract: This study was aimed to investigate the effects of docetaxel on proliferation and apoptosis of multiple myeloma cell line RPMI8226 and its mechanism. The inhibitory rate of multiple myeloma cells was detected by MTT, the morphological and ultrastructural changes of RPMI8226 cells were observed by using inverted fluorescent microscope and transmission electron microscope, the apoptosis-inducing effect of docetaxel on RPMI-8226 cells was determined by flow cytometry with Annexin-V FITC/PI staining, the cell distribution in cell cycle of RPMI-8226 cells was assayed using flow cytometry with PI staining; the effect of docetaxel on expression of BCL-2, caspase-8, caspase-3 mRNA was detected by semiquantitative RT-PCR, the expression changes of BCL-2 protein in RPMI-8226 cells before and after treatment with docetaxel were measured by using Western blot. The results indicated that 0.25 - 8.0 µg/ml docetaxel obviously inhibited the proliferation of RPMI-8226 cells in both time- and dose-dependent manners. Cell number of docetaxel-treated group was significantly less than control group under inverted fluorescent microscope, and the cell arrangement was irregular, necrotic cells could be seen occasionally. By transmission electron microscope, the morphological and ultrastructural changes of cell typical apoptosis could be observed, a few necrotic cells could be captured, too. Compared with control group, docetaxel induced the apoptosis of RPMI-8226 cell line (P < 0.01). Docetaxel mainly arrested RPMI-8226 cells in the G(2)/M phase (P < 0.01). The expression of BCL-2 mRNA decreased (P < 0.05), while the mRNA expression of caspase-8 and caspase-3 increased (P < 0.05). Western blot indicated that BCL-2 protein expression also decreased (P < 0.05). It is concluded that docetaxel can inhibit the proliferation of RPMI-8226 cells by inducing cell apoptosis. Activation of the mitochondrial and death receptor pathways of apoptosis may be involved in the docetaxel-induced apoptosis, cell cycle arrest may also play an important role in the apoptosis mechanism.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Bao-Lan
authors.initials: BL
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Mei-Ying
authors.initials: MY
authors.lastname: Qi
authors.forename: Nai-Cen
authors.initials: NC
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000077143:Docetaxel; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D000077143:Docetaxel; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8