Objective To systematically review the effectiveness and safety of arsenic trioxide (ATO) versus retinoic acid for patients with acute promyelocytic leukemia (APL). Methods Such databases as PubMed, The Cochrane Library (Issue 12, 2012), CNKI, WanFang Data and VIP were electronically and comprehensively searched from inception to December 2012, for randomized controlled trials (RCTs) on the effectiveness and safety of ATO versus retinoic acid for patients with APL. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Then, meta-analysis was performed using RevMan 5.0.2 software. Results Eight RCTs involving 586 cases of APL patients. The results of meta-analysis showed that, ATO and all-trans-retinoic (ATRA) were not statistically different in CR rates (OR=0.85, 95%CI 0.54 to 1.35, P=0.50), CR time (OR=–8.14, 95%CI –16.42 to 0.13, P=0.05), recurrence rates (OR=0.14, 95%CI 0.02 to 1.21, P=0.07), early mortality (OR=0.82, 95%CI 0.32 to 2.06, P=0.67), and five-year total survival rates (OR=1.19, 95%CI 0.54 to 2.60, P=0.66). ATO had lower incidences of adverse reaction such as hyperleukocytosis syndrome (OR=0.32, 95%CI 0.18 to 0.58, P=0.000 1) and retinoic acid syndrome (OR=0.05, 95%CI 0.02 to 0.14, Plt;0.000 01). Conclusion ATO and ATRA are alike in CR rates, CR time, recurrence rates, early mortality, and five-year total survival rates, but ATO causes less adverse reaction. Due to the limited quantity and quality of the included studies, ATO should be applied with caution according to patients’ conditions in clinic.
Objective To assess the clinical effectiveness and safety of inductive treatment with arsenic trioxide （As203） for acute promyelocytic leukemia （APL）. Methods Randomized controlled trials （RCTs） were identified from MEDLINE （1966 -July, 2005 ）, EMBASE （1984 -July, 2005 ）, The Cochrane Library （ Issue 3, 2005） and CBM- disc （1978 -July, 2005）. The references of eligible studies were handsearched. RCTs of As203 treating for APL were included. Data were evaluated and extracted by two reviewers independently with designed extraction form. RevMan 4. 2.7 software was used for data analysis. Results Six RCTs involving 323 patients were included. Two studies reported that there was no statistical difference between As2O3 group and all-transretinoic acid （ATRA） group in mortality for patients with APL or APL patients with complications of desseminated intiavascular coagulation or cerebra hemorrhage. The pooled result of 4 studies showed that there was no statistical difference with RR 0.98, 95 % CI 0.86 to 1.12 in complete remission （CR） rates between the two groups. The result of one study showed that the CR rate of patients with intravenous injection of As203 in 2 divided dosages with longer injection duration was higher with RR 1.31, 95% CI 0.86 to 1.12 compared with those with a single intravenous injection. Adverse effects in As2O3 group were less than ATRA group. Conclusions Inductive treatment with As2O3 for acute promyelocytic leukeuia has similar mortality and CR with less adverse effects compared with ATRA. More trials of high quality are required.
Objective To observe the effect of a wide range of concentration of arsenic trioxide on hepatoma cell line BEL-7402 with variable duration. Methods The cell activity and morphologic changes were studied after treated with different concentration. The apoptosis were detected by flow cytometry assay and DNA Gel electrophoresis. Results The effect of arsenic trioxide on hepatoma cell lines were dependent on the time and concentration obviously. Hepatoma cells cultured with different concentration presented apoptosis features: i.e. intact cell membrane, chromatin condensation, nucleic fragmentation and apoptotic body formation; flow cytometry analysis showed an arrestment at G2/M phase and a subG1 cell peak, DNA gel electrophoresis showed a marked DNA ladder. Conclusion Arsenic trioxide can obviously inhibit the growth of hepatoma cell lines through inducing hepatoma cell apoptosis.
【Abstract】Objective To study the effects of arsenic trioxide (As2O3) on inhibiting the proliferation of hepatic carcinoma cell lines. Methods To detect the inhibiting rate of As2O3 and other 6 kinds of anticancer drugs (such as, NOV, ADM, MMC, 5-Fu, DDP and CTX) on hepatic carcinoma cell lines BEL-7404 and SMMC-7721 by using MTT assay. Results As compared with other 6 kinds of anticancer drugs, the inhibiting rate of As2O3 was the highest one (P＜0.01 or P＜0.05). The inhibiting rates of As2O3 in the groups with the concentration above 1.0 μg/ml were no different (P＞0.05). Conclusion As2O3 could inhibit hepatic carcinoma cell lines BEL-7404 and SMMC-7721 effectively in vitro. Drug sensitivity tests of different concentration’s As2O3 should be done in order to select the minimal and effective concentration of arsenic trioxide and reduce the side effects of arsenic trioxide.
Objective To observe the outcomes of using different concentrations of arsenic trioxide at varying phases on the breast cancer cell line MCF-7 and to study the mechanism of this effect. Methods The effect of arsenic trioxide on the growth of breast cancer cell line MCF-7 was observed after applying arsenic trioxide of different concentrations （0.5-16 μmol/Ｌ）. The inhibitory effect of arsenic trioxide on the cell proliferation was investigated with 3-(4，5-dimethyl-thizazol-2-yl)-2， 5-diphenyl tetrazolium bromide (MTT) and the induction of arsenic trioxide on cell apoptosis was detected by DNA ladder and terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL). Results The effect of arsenic trioxide on breast cancer cell line MCF-7 depended on the phase and the dose. The number of cell decreased significantly and there were conspicuously typical morphological changes of apoptosis after the use of arsenic trioxide， including membrane blebbing， chromatin pyknosis, nuclear fragmentation and the formation of apoptotic body. The typical DNA ladders were observed in the MCF-7 cells after 48 h administration of arsenic trioxide at concentrations 1-8 μmol/Ｌ. Significant elevations of apoptosis index at 24 h, 48 h and 72 h were all detected by TUNEL after incubating with 4 μmol/L arsenic trioxide. Conclusion Arsenic trioxide may inhibit the growth of breast cancer cell line MCF-7 significantly by inducing the apoptosis of breast cancer cell.
【Abstract】ObjectiveTo investigate the effects of As2O3 on expression of NF-κB p65, survivin and caspase-3 in human breast infiltrating duct carcinoma xenograft model on nude mice. Methods A human breast infiltrating duct carcinoma model on nude mice was established and the nude mice were divided randomly into three groups: control group, DDP group and As2O3 group （1.5 and 3.0 mg/kg concentrations）. The expression of survivin mRNA was detected with the method of in situ hybridization and the expressions of NF-κB p65, survivin and caspase-3 protein were measured with immunohistochemistry. ResultsThe positive rates of NF-κB p65 and survivin expression were higher in the control group than those in the DDP group and the As2O3 groups, but that of caspase-3 was on the opposite way (P＜0.01). The positive rates of NF-κB p65 and survivin in As2O3 group were negatively related with the concentrations of As2O3 (P＜0.01), but that of caspase-3 was on the opposite way (P＜0.01). The expressions of NF-κB p65 and survivin protein were positively correlated with that of survivin mRNA, but any of them was negatively correlated with the expression of caspase-3 protein. ConclusionAs2O3 inhibites survivin probably by inhibiting the activity of NFκB p65 and subsequently activates caspase-3, which induces apoptosis of human breast infiltrating duct carcinoma cells and is in a dose-dependent manner.