title: [Mechanism associated to enhancing the sensitivity of myeloma cells U266 to bortezomib by 2-methoxyestradiol].
abstract: This study was aimed to explore the synergistic effect of 2-methoxyestradiol (2-ME2) and bortezomib (Bor) on the proliferative inhibition and apoptosis of U266 cell line and its possible mechanism. The cells were treated with 2-ME2, Bor alone and 2-ME2 combined with Bor, respectively. The cell viability and proliferative curve were detected by CCK8, the cell apoptosis was detected by caspase 3/7 activity test, cell cycle status was analyzed by flow cytometry, and real-time PCR was used to detect the mRNA expression of P21, BAX and BCL-2. The results showed that compared with cells treated with 2-ME2 or Bor alone, the proliferative potential of cells in combination group was significantly inhibited (p < 0.05), and apoptosis rate markedly increased (p < 0.05), cell cycle was arrested at G(1)-S phase, the mRNA expressive level of P21 and BAX increased, while the expression of BCL-2 decreased. It is concluded that 2-ME2 combined with Bor synergistically inhibits cell proliferation and induces apoptosis in U266 cell line. The possible mechanism may be associated with its effect of up-regulating P21 and BAX expressions.
authors.affiliation: Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
authors.forename: Shun-Quan
authors.initials: SQ
authors.lastname: Wu
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Xu
authors.forename: Hao-Bo
authors.initials: HB
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.forename: Rong
authors.initials: R
authors.lastname: Zhan
mesh_terms: D000077584:2-Methoxyestradiol; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D011719:Pyrazines / Q000494:pharmacology*
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D004958:Estradiol; D000069286:Bortezomib; D000077584:2-Methoxyestradiol