Objective To investigate the possible mechanism of arsenic trioxide (As2O3) inducing P16 gene demethylation and transcription regulation in the retinoblastoma (RB) Cell Line Y79． Methods The induced growth inhibition of Y79 cell was assayed by MTT; The DNA content of Y79 cell was analyzed by flow cytometry after being exposed to As2O3; the methylation status of the P16 gene in Y79 cell line before and after treatment with As2O3 was detected by the nestedmethylation specific PCR and DNA sequencing; the mRNA of P16,DNA methyltransferases (DNMT3A and 3B)gene were determined by RT-PCR． Results As2O3 was able to inhibit the growth of Y79 cell and increase the cell number in G0-G1 phase；P16 gene was not expressed in Y79 cell line and As2O3 can induce itrsquo;s mRNA expression；after 48 hour disposal of As2O3，the methylation levelof P16 gene was apparently attenuated in Y79 cell line,the expression of DNMT3A and DNMT3B was obviously down-regulated． Conclusions P16 gene is the hypermethylation in the retinoblastoma cell line Y79, and As2O3 can inhibite the methylation of P16 gene and upregulate the expression of p16 gene mRNA which inhibits the proliferation of Y79 cell by inducing the G0-G1 arrest, by inhibiting the expression of DNA methyltransferases.
ObjectiveTo systematically review the effectiveness and safety of demethylation agents in patients with myelodysplastic syndrome. MethodsRandomized controlled trials (RCTs) about demethylation agents in treating myelodysplastic syndrome was electronically searched in PubMed, EMbase, The Cochrane Library (Issue 3, 2013), Web of Science, CNKI, VIP, WanFang Data and CBM from inception to March 2013. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of the included studies. Meta-analysis was performed using RevMan 5.1 software. ResultsA total of 4 studies involving 816 patients were finally included. The results of meta-analysis showed that:for patients with myelodysplastic syndrome at middle/advanced stage, compared with the best supportive treatment plan, demethylation agents improved complete remission (CR) (OR=19.14, 95%CI 5.33 to 68.7, P < 0.000 01), partial remission (PR) (OR=20.63, 95%CI 5.76 to 73.93, P < 0.000 01), hematological improvement (HI) (OR=3.58, 95%CI 2.40 to 5.34, P < 0.000 01), and the incidences of Grade Ⅲ or Ⅳ neutropenia (OR=3.82, 95%CI 2.67 to 5.47, P < 0.000 01), Grade Ⅲ or Ⅳ thrombocytopenia (OR=3.98, 95%CI 2.55 to 6.23, P < 0.000 01), and mortalities (OR=0.52, 95%CI 0.35 to 0.77, P < 0.000 01), all with significant differences; and part of patients suffered from Grade Ⅲ or Ⅳ thrombocytopenia and tolerable adverse reaction caused by non-hematologic change. ConclusionCurrent evidence suggests that demethylation agents in treating myelodysplastic syndrome have apparently curative effects. Besides, it could prolong the time of turning into acute myelocytic leukemia, reduce mortalities, and improve patients' quality of life.