[Investigation of the effect of 2-methoxyestradiol and arsenic trioxide on the apoptosis-associated gene expression profile of myeloma cells].
OBJECTIVE
To explore the effect of 2-methoxyestradiol (2ME2) and arsenic trioxide (As2O3) on the apoptosis related gene expression in multiple myeloma cell line CZ-1.


METHODS
Total RNA was isolated from CZ-1 cells which had been treated with 2ME2 and As2O3 at an apoptosis-inducing concentration and reverse-transcribed into a cDNA probe labeled with Bio-16-dUTP, and then hybridized it with a microarray containing up to 96 key genes involved in apoptosis. The gene expression profile of the 2ME2 and As2O3 treated CZ-1 cells were analyzed with GEArray Analyzer software. The microarray results were confirmed by RT-PCR.


RESULTS
As2O3 treatment caused the alteration in the expression of 52 genes (54.2% of total genes on microarray). Among them, 42 (80.8%) were upregulated and 10 (19.2%) were downregulated. The upregulated genes were mainly involved in caspases family, P53 and ATM pathway, death effector domain family, TNF receptor family and CIDE family. 2ME2 treatment resulted in the alteration of 42 genes (43.8% of the total genes on microarray). Of them, 32 (76.2%) were downregulated and 10 (23.8%) were upregulated. The downregulated genes mainly belonged to bcl-2 family, inhibitor of apoptosis protein family (IAP), TRAF family, TNF ligand family, and CARD family.


CONCLUSIONS
2ME2 and As2O3 induce the CZ-1 cells apoptosis by different pathways. As2O3 mainly induces upregulation of proapoptotic genes, and 2ME2 downregulation of anti-apoptotic genes expression.
Xiong
Hong
H
Department of Hematology, Changzheng Hospital, Second Military Medical College, Shanghai 200003, China.
Hou
Jian
J
Gao
Wei-Ran
WR
Chen
Qu-Bo
QB
D000077584:2-Methoxyestradiol; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010087:Oxides / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050257:Tubulin Modulators / Q000494:pharmacology
D001152:Arsenicals; D010087:Oxides; D050257:Tubulin Modulators; D004958:Estradiol; D000077584:2-Methoxyestradiol; D000077237:Arsenic Trioxide