[Correlation of cell cycle alteration to SOCS-1 gene demethylation induced by arsenic trioxide in myeloma cell lines].
OBJECTIVE
Recent studies suggest strong therapeutic potentials of arsenic trioxide (As2O3) for multiple myeloma(MM), which may be due to As2O3-induced demethylation of tumor suppressor genes. This study was to explore the correlation of cell cycle alteration to SOCS-1 gene demethylation after As2O3 induction in MM cell lines in vitro.


METHODS
MM cell lines U266 and RPMI8226 were used. Cell proliferation and cell cycle of MM cells after the treatment of As2O3 were assessed by MTT assay and flow cytometry, respectively. Methylation status was detected by methylation specific PCR (MSP-PCR), and gene expression of SOCS-1 was measured by real-time PCR in MM cells before and after As2O3 treatment.


RESULTS
As2O3 significantly inhibited the growth of U266 and RPMI8226 cells in a dose-dependent manner. The cell cycle of U266 and RPMI8226 were arrested at G0/G1 phase. Compared with the wild type, the percentage of cells was increased at G0-G1 phase, but decreased at S phase after the treatment of As2O3 for 72 h (P < 0.05). The mRNA expression of SOCS-1 gene was significantly increased with hemi-methylation (As2O3, 0.5 micromol/L,72 h) or complete demethylation (As2O3, 1.0 micromol/L or As2O3, 2.0 micromol/L,72 h) of the SOCS-1 gene in comparison with the wide type (P<0.05).


CONCLUSIONS
As2O3 could induce cell cycle alteration of MM, which might be related to demethylation and reexpression of SOCS-1 gene in MM cell lines. The study might provide a new approach to elucidate the mechanism of the antitumor effect of As2O3 in MM.
Wang
Ming-Ming
MM
Department of Hematology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Hematology, Shanghai, China.
Dou
Hong-Ju
HJ
Zou
Li-Fang
LF
Zhu
Qi
Q
Ren
Zhi-Hong
ZH
Hu
Jun-Pei
JP
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D012333:RNA, Messenger; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000077237:Arsenic Trioxide