[Effect of 2-methoxyestradiol on proliferation and apoptosis of myeloma cell lines].
The objective was to explore the in vitro effects of growth inhibition and apoptosis induction of 2-methoxyestradiol (2ME2), an estrogen derivative, on seven myeloma cell lines NCI-H929, HS-sultan, KM3, SKO-007, CZ-1, U266 and LP-1and to observe its synergistic effects in combination with some other drugs, such as dexamethasone, As(2)O(3), thalidomide and zoledronic acid. Seven myeloma cell lines NCI-H929, HS-sultan, KM3, SKO-007, CZ-1, U266 and LP-1 were cultured at different concentrations with or without dexamethasone, As(2)O(3), thalidomide and zoledronic acid. Cell viability was assessed by trypan blue assay, plasma cell labeling index (PCLI) was detected by BrdU assay, terminal-deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay were used to determine apoptosis cells in situ. Synergistic effects of 2ME2 in combination with other drugs were judged by King's formula. The results showed that after treatment with 1, 4, 8, 12, 16 micromol/L 2ME2 at 12, 24, 36 and 48 hours respectively, 2ME2 caused a dose- and time-dependent inhibition of the cell viability. The concentration of 50% growth inhibition (IC(50)) was between (20.8 +/- 0.27) and (34.1 +/- 0.57) micromol/L. After treatment with 12 micromol/L 2ME2 within 24 hours, 2ME2 led to a progressive decline in the fraction of S-phase cells by BrdU assay, plasma cell labeling index (PCLI) declined from (30.14 +/- 4.28)% to (14.71 +/- 6.27)% (P < 0.05). After treatment with 1, 4, 8, 12, 16 micromol/L 2ME2 at 12, 24, 36 and 48 hours respectively, 2ME2 can induce a dose- and time-dependent apoptosis of myeloma cell lines. The percentage of apoptosis was between 9% - 33% (P < 0.05). Q value of synergistic effects was between 1.13 to 1.43. It is concluded that 2ME2 can inhibit proliferation and induce apoptosis of myeloma cell lines and has synergistic effects with dexamethasone, As(2)O(3), thalidomide and zoledronic acid.
Gao
Wei-Ran
WR
Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China.
Hou
Jian
J
D000077584:2-Methoxyestradiol; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology; D010087:Oxides / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D001152:Arsenicals; D010087:Oxides; D004958:Estradiol; D000077584:2-Methoxyestradiol; D003907:Dexamethasone; D000077237:Arsenic Trioxide