INTRODUCTION Cell apoptosis,which involves the biologic regulation of the numbers and vital activity of cells,is an important metaboloc process in both normal cells and tumor cells.
Objective： To investigate the apoptosis induction by arsenic trioxide （As2O3） in Raji cells and its correlation with cell cycle arrest and expression of the Survivin gene. Methods： After Raji cells were treated wi...Objective： To investigate the apoptosis induction by arsenic trioxide （As2O3） in Raji cells and its correlation with cell cycle arrest and expression of the Survivin gene. Methods： After Raji cells were treated with As2O3 in different concen- trations （1, 2, 4 and 8 pM）, for 24, 48 and 72 h, respectively, and cell proliferation was tested by MTT assay. Apoptosis was observed with electron microscope and DNA electrophoresis. The distribution of cell cycles and cell apoptosis were detected by flow cytometry. Expression of the Survivin gene was determined by real-time quantitative RT-PCR. Results： As2O3 （1-8 μM） inhibited Raji cells growth effectively in a dose- and time-dependent manner. As2O3 at 2-8μM could induce cell apoptosis and cell cycle arrest. However, As2O3（1 μM） inhibited Raji proliferation only by cell cycle arrest, without any symptoms of cell apoptosis. At the same time, Survivin gene expression was down-regulated after the treatment. Conclusion： As2O3 could induce substantial proliferation inhibition, cell cycle arrest and apoptosis in Raji cell. Cell cycle arrest might be a reason why apoptosis occurs. As2O3 can markedly down-regulate expression of the Survivin gene in a dose- and timedependent manner. The down-regulated Survivin gene might be leading to cell apoptosis by As2O3.展开更多
Objective： The aim of the study was to investigate the prospective study if treatment with arsenic trioxide （AS2O3） could enhance disease-free survival as adjuvant post-operative chemotherapy for gastric cancer pat...Objective： The aim of the study was to investigate the prospective study if treatment with arsenic trioxide （AS2O3） could enhance disease-free survival as adjuvant post-operative chemotherapy for gastric cancer patients and protect bone marrow from the negative effects of chemotherapy. Methods： 84 adults were randomized into two groups. Patients in treament group were treated with As2O3 and FOLFOX regimen, the other were administered with FOLFOX regimen only. Results： Four patients were withdrawn in treatment group after 3-4 cycles and the reasons were headache and fidgety （n = 2）, rhythmia （n = 1） and AST/ALT elevation （n = 1）, while 1 patient in control group after 4 cycles for neutropenia. In the treatment group, the median DFS was 28.34 months （95% CI, 25-33 months）. While in control group, the median DFS was 24.50 months （95% CI, 20-30 months）. This difference was not statistically significant （chi-square： 2.8885; P value： 0.0892）. Pa- tients in the same subgroup of node-positive was 29 in the treatment group and 32 in control group, respectively. The median DFS was 27.87 months （95% CI, 25-31 months） in the treatment group and 24.18 months （95% CI, 19-31 months） in the control group with promising statistical significance （HR 1.89; chi-square： 4.78; P value： 0.0287）. The most common grades 3-4 toxicity was leucopenia （n = 11） in control group and the difference was significant （chi-square： 3.9768, P value： 0.046） compared with that in treatment group （n = 4）. Conclusion： The combination of arsenic trioxide and FOLFOX regimen has a potential advantage of enhancing disease-free survival in patients with gastric cancer in nodal-positive status as post-operative chemotherapy, and protect bone marrow from the negative effects of chemotherapy.展开更多
Objective To evaluate the effects of arsenic trioxide (As-2O-3) on apoptosis and differentiation of gastric cancer cell lines (GCCL). Methods MKN45 and SGC7901 cells were treated with As-2O-3 at different concentratio...Objective To evaluate the effects of arsenic trioxide (As-2O-3) on apoptosis and differentiation of gastric cancer cell lines (GCCL). Methods MKN45 and SGC7901 cells were treated with As-2O-3 at different concentrations, then the apoptosis rates and cell cycle were determined by flow cytometry assays, the morphologic changes were observed under fluorescence microscopy and electronic microscopy, and the gene expressions were tested with immunohistologic staining. Results Higher apoptosis rates of GCCL were seen in the As-2O-3-treated group at concentrations of 5μmol and 10μmol, as compared with those in the 5-Fu-treated group. Cell-nuclear pyknosis and chromosomal condensation were observed. The As-2O-3 at a concentration of 0.5 μmol could induce the cell cycle changes of GCCL, revealing an increase in the proportion of G1/G0 phase cells and a decrease in the proportion of S phase cells. From the fifth day after treatment of SGC7901 with As-2O-3 at a low concentration, P53 and bcl-XL genes expression rates were reduced, Bax gene expression rate increased, and bcl-2 gene expression showed little change. Conclusion As-2O-3 could induce GCCL apoptosis at a high concentration and differentiation at a low concentration, but it could not completely reverse the malignant biological behaviours of cancer cells.展开更多
It was recently reported that arsenic trioxide (As2O3) can induce complete remission in patients with acute promyelocytic leukemia (APL). In this present article, the biological effect of As203 on human cervical cance...It was recently reported that arsenic trioxide (As2O3) can induce complete remission in patients with acute promyelocytic leukemia (APL). In this present article, the biological effect of As203 on human cervical cancer HeLa cells and HeLa cells overexpressing Bcl-2 is studied. By MTT and colony forming ability assays, morphology alteration, flow cytometric analysis, DNA gel electrophoresis and in situ cell death detection (TUNEL) , it was found that As2O3 inhibited the growth of HeLa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR, Northern blot, Western blot analysis revealed that As2O3 induced HeLa cell apoptosis possibly via decreasing the expression of c-myc and viral genes. HeLa cells overexpressing Bcl-2 partly resist As2O3 induced apoptosis, which might be relative to preventing the cells from As2O3 caused G2/M block, downregulation of c-myc gene expression and inhibition of viral gene expression was also noted. However, it was found that As2O3 at a high concentration could also induce apoptosis of HeLa cells over-expressing Bcl-2 possibly mainly via downregulating Bcl-2 expression and slightly inhibiting viral gene expression.展开更多
Objective To study the effect of arsenic trioxide (As 2O 3) on non APL acute myeloid leukemia (AML) cells and the interreactive effect between retinoic acid (RA) and As 2O 3 Methods RA sensitive (S) and RA ...Objective To study the effect of arsenic trioxide (As 2O 3) on non APL acute myeloid leukemia (AML) cells and the interreactive effect between retinoic acid (RA) and As 2O 3 Methods RA sensitive (S) and RA resistant (R) HL 60 non APL AML cells were used as an in vitro model Cell number and trypan blue were used to observe cell growth and survival Apoptosis was determined by morphological changes, using a DNA laddering assay, terminal deoxynucleotidyl transferase (TdT) fragment end labeling assay and a flow cytometry assay Results As 2O 3 induced apoptosis in both HL 60S and HL 60R cells, As 2O 3 induced apoptosis was both time and concentration dependent in a therapeutically achievable As 2O 3 range (0 25-4.0?μmol/L) Both all trans retinoic acid (ATRA) and 9 cis retinoic acid (9cRA) potentiated As 2O 3 induced apoptosis, as measured by quantitative TdT fragment end labeling and flow cytometry assays in both HL 60S and HL 60R cells ( P <0 05, for all RA+As 2O 3 combinations vs As 2O 3 alone in both sublines) Conclusions As 2O 3 may inhibit the growth of non APL AML cells by promoting programmed cell death RA can potentiate As 2O 3 induced apoptosis even in RA resistant HL 60 cells in which the classical ATRA response pathway is repressed owing to a homozygous inactivating mutation in the retinoic acid receptor α As 2O 3 can have clinical activity in non APL cases of AML and the enhanced activity might result from the combined As 2O 3 RA therapy展开更多
A comprehensive theoretical study on the bimolecular reaction of C2H502 with OH radicals was performed at the CCSD（T）/6-311＋＋G（2df2p）//B3LYP/6-311＋G（d,p） level of theory. The calculation results show that C2H...A comprehensive theoretical study on the bimolecular reaction of C2H502 with OH radicals was performed at the CCSD（T）/6-311＋＋G（2df2p）//B3LYP/6-311＋G（d,p） level of theory. The calculation results show that C2H5O2 ＋ OH reaction proceeds on both the singlet and the triplet potential energy surfaces（PESs）. On the singlet PES, the favorable pathway is the addition of OH radical to the terminal oxygen atom of C2H5O2 radical, leading to the formation of trioxide C2H5O3H with a barrierless process. Then, the trioxide directly decomposes to the products C2H50 and HO2 radicals. On the triplet PES, the predominant pathways are a and β hydrogen atom abstractions of C2H5O2 radical by OH radical-forming products 3CH3CHO2＋H2O and 3CH2CH2O2＋H2O, and the corresponding bar- tiers are 12.02（3TS8） and 19.19 kJ/mol（3TS9）, respectively. In addition, the comprehensive properties of trioxide C2H503H were investigated for the ftrst time. The results indicate that the trioxide complex RC1 can exist stably in the atmosphere owing to a significantly large and negative enthalpy of formation（-118.44 kJ/mol） as well as a high first excitation energy（5.94 eV）.展开更多
文摘INTRODUCTION Cell apoptosis,which involves the biologic regulation of the numbers and vital activity of cells,is an important metaboloc process in both normal cells and tumor cells.
基金a grand from the Educational Committee Scientific Research Foundation of Yunnan Province. (No. 06z095c).
文摘Objective： To investigate the apoptosis induction by arsenic trioxide （As2O3） in Raji cells and its correlation with cell cycle arrest and expression of the Survivin gene. Methods： After Raji cells were treated with As2O3 in different concen- trations （1, 2, 4 and 8 pM）, for 24, 48 and 72 h, respectively, and cell proliferation was tested by MTT assay. Apoptosis was observed with electron microscope and DNA electrophoresis. The distribution of cell cycles and cell apoptosis were detected by flow cytometry. Expression of the Survivin gene was determined by real-time quantitative RT-PCR. Results： As2O3 （1-8 μM） inhibited Raji cells growth effectively in a dose- and time-dependent manner. As2O3 at 2-8μM could induce cell apoptosis and cell cycle arrest. However, As2O3（1 μM） inhibited Raji proliferation only by cell cycle arrest, without any symptoms of cell apoptosis. At the same time, Survivin gene expression was down-regulated after the treatment. Conclusion： As2O3 could induce substantial proliferation inhibition, cell cycle arrest and apoptosis in Raji cell. Cell cycle arrest might be a reason why apoptosis occurs. As2O3 can markedly down-regulate expression of the Survivin gene in a dose- and timedependent manner. The down-regulated Survivin gene might be leading to cell apoptosis by As2O3.
基金Supported by a grant from the Harbin Technologies R&D Program of China (No.2004AA9CS196-9)
文摘Objective： The aim of the study was to investigate the prospective study if treatment with arsenic trioxide （AS2O3） could enhance disease-free survival as adjuvant post-operative chemotherapy for gastric cancer patients and protect bone marrow from the negative effects of chemotherapy. Methods： 84 adults were randomized into two groups. Patients in treament group were treated with As2O3 and FOLFOX regimen, the other were administered with FOLFOX regimen only. Results： Four patients were withdrawn in treatment group after 3-4 cycles and the reasons were headache and fidgety （n = 2）, rhythmia （n = 1） and AST/ALT elevation （n = 1）, while 1 patient in control group after 4 cycles for neutropenia. In the treatment group, the median DFS was 28.34 months （95% CI, 25-33 months）. While in control group, the median DFS was 24.50 months （95% CI, 20-30 months）. This difference was not statistically significant （chi-square： 2.8885; P value： 0.0892）. Pa- tients in the same subgroup of node-positive was 29 in the treatment group and 32 in control group, respectively. The median DFS was 27.87 months （95% CI, 25-31 months） in the treatment group and 24.18 months （95% CI, 19-31 months） in the control group with promising statistical significance （HR 1.89; chi-square： 4.78; P value： 0.0287）. The most common grades 3-4 toxicity was leucopenia （n = 11） in control group and the difference was significant （chi-square： 3.9768, P value： 0.046） compared with that in treatment group （n = 4）. Conclusion： The combination of arsenic trioxide and FOLFOX regimen has a potential advantage of enhancing disease-free survival in patients with gastric cancer in nodal-positive status as post-operative chemotherapy, and protect bone marrow from the negative effects of chemotherapy.
文摘Objective To evaluate the effects of arsenic trioxide (As-2O-3) on apoptosis and differentiation of gastric cancer cell lines (GCCL). Methods MKN45 and SGC7901 cells were treated with As-2O-3 at different concentrations, then the apoptosis rates and cell cycle were determined by flow cytometry assays, the morphologic changes were observed under fluorescence microscopy and electronic microscopy, and the gene expressions were tested with immunohistologic staining. Results Higher apoptosis rates of GCCL were seen in the As-2O-3-treated group at concentrations of 5μmol and 10μmol, as compared with those in the 5-Fu-treated group. Cell-nuclear pyknosis and chromosomal condensation were observed. The As-2O-3 at a concentration of 0.5 μmol could induce the cell cycle changes of GCCL, revealing an increase in the proportion of G1/G0 phase cells and a decrease in the proportion of S phase cells. From the fifth day after treatment of SGC7901 with As-2O-3 at a low concentration, P53 and bcl-XL genes expression rates were reduced, Bax gene expression rate increased, and bcl-2 gene expression showed little change. Conclusion As-2O-3 could induce GCCL apoptosis at a high concentration and differentiation at a low concentration, but it could not completely reverse the malignant biological behaviours of cancer cells.
文摘It was recently reported that arsenic trioxide (As2O3) can induce complete remission in patients with acute promyelocytic leukemia (APL). In this present article, the biological effect of As203 on human cervical cancer HeLa cells and HeLa cells overexpressing Bcl-2 is studied. By MTT and colony forming ability assays, morphology alteration, flow cytometric analysis, DNA gel electrophoresis and in situ cell death detection (TUNEL) , it was found that As2O3 inhibited the growth of HeLa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR, Northern blot, Western blot analysis revealed that As2O3 induced HeLa cell apoptosis possibly via decreasing the expression of c-myc and viral genes. HeLa cells overexpressing Bcl-2 partly resist As2O3 induced apoptosis, which might be relative to preventing the cells from As2O3 caused G2/M block, downregulation of c-myc gene expression and inhibition of viral gene expression was also noted. However, it was found that As2O3 at a high concentration could also induce apoptosis of HeLa cells over-expressing Bcl-2 possibly mainly via downregulating Bcl-2 expression and slightly inhibiting viral gene expression.
文摘Objective To study the effect of arsenic trioxide (As 2O 3) on non APL acute myeloid leukemia (AML) cells and the interreactive effect between retinoic acid (RA) and As 2O 3 Methods RA sensitive (S) and RA resistant (R) HL 60 non APL AML cells were used as an in vitro model Cell number and trypan blue were used to observe cell growth and survival Apoptosis was determined by morphological changes, using a DNA laddering assay, terminal deoxynucleotidyl transferase (TdT) fragment end labeling assay and a flow cytometry assay Results As 2O 3 induced apoptosis in both HL 60S and HL 60R cells, As 2O 3 induced apoptosis was both time and concentration dependent in a therapeutically achievable As 2O 3 range (0 25-4.0?μmol/L) Both all trans retinoic acid (ATRA) and 9 cis retinoic acid (9cRA) potentiated As 2O 3 induced apoptosis, as measured by quantitative TdT fragment end labeling and flow cytometry assays in both HL 60S and HL 60R cells ( P <0 05, for all RA+As 2O 3 combinations vs As 2O 3 alone in both sublines) Conclusions As 2O 3 may inhibit the growth of non APL AML cells by promoting programmed cell death RA can potentiate As 2O 3 induced apoptosis even in RA resistant HL 60 cells in which the classical ATRA response pathway is repressed owing to a homozygous inactivating mutation in the retinoic acid receptor α As 2O 3 can have clinical activity in non APL cases of AML and the enhanced activity might result from the combined As 2O 3 RA therapy
基金Supported by the National Natural Science Foundation of China（Nos.21473108, 21473107） and the Fundamental Research Funds for the Central Universities of China（No.GK201603035）.
文摘A comprehensive theoretical study on the bimolecular reaction of C2H502 with OH radicals was performed at the CCSD（T）/6-311＋＋G（2df2p）//B3LYP/6-311＋G（d,p） level of theory. The calculation results show that C2H5O2 ＋ OH reaction proceeds on both the singlet and the triplet potential energy surfaces（PESs）. On the singlet PES, the favorable pathway is the addition of OH radical to the terminal oxygen atom of C2H5O2 radical, leading to the formation of trioxide C2H5O3H with a barrierless process. Then, the trioxide directly decomposes to the products C2H50 and HO2 radicals. On the triplet PES, the predominant pathways are a and β hydrogen atom abstractions of C2H5O2 radical by OH radical-forming products 3CH3CHO2＋H2O and 3CH2CH2O2＋H2O, and the corresponding bar- tiers are 12.02（3TS8） and 19.19 kJ/mol（3TS9）, respectively. In addition, the comprehensive properties of trioxide C2H503H were investigated for the ftrst time. The results indicate that the trioxide complex RC1 can exist stably in the atmosphere owing to a significantly large and negative enthalpy of formation（-118.44 kJ/mol） as well as a high first excitation energy（5.94 eV）.
