Objective: To elucidate the pattern of chemo therapy drugs induced apoptosis and its role in chemo therapy of acute leukemia. Methods: Apoptosis induced by Ara C in human myeloid leukemia cell line HL 60 was inve...Objective: To elucidate the pattern of chemo therapy drugs induced apoptosis and its role in chemo therapy of acute leukemia. Methods: Apoptosis induced by Ara C in human myeloid leukemia cell line HL 60 was investigated by applying light microscope, electron microscopy combined with DNA electrophoresis and flow cytometry analysis techniques. Results: Apoptosis per sisted throughout 36 h following addition of Ara C with a gradual augmentation. Efficiency of apoptosis was enhanced in a dosedependent pattern, HL 60 treated with six other chemotherapy drugs and peripheral white blood cells from a AML case undergoing DA regimen chemo therapy exhibited typical DNA ladder pattern. Further investigation indicated that chemotherapy drugs apop tosis came into being possibly by downregulating the expression of c myc and bcl 2 oncogenes. Conclusion: Chemotherapy induced apoptosis is the primary mecha nism of chemotherapy.展开更多
The myeloid leukemic cell line HL-60 was studied by using DNA gel electrophoresis, flow cytomery, McAb C-myc, McAb Bc1-2 and CFU-L. From zero to 36 h,the apoptosis rates of 8 different phases and other indexes were ob...The myeloid leukemic cell line HL-60 was studied by using DNA gel electrophoresis, flow cytomery, McAb C-myc, McAb Bc1-2 and CFU-L. From zero to 36 h,the apoptosis rates of 8 different phases and other indexes were observed. The results showed that with the prolonged time of drug incubation,apoptosis of HL-60 cells increased progressively. This effect can be enhanced obviously by rh-IL-3 and rh-GM-CSF. At the same time,the killed rate of leukemic cells by Ara-C induction was increased. C-myc expression was decreased and Bc1-2 expression did not display apparent change. Interestingly, the normal hemopoietic cells were not affected by these two kinds of cytokine. The theoretical basis was provided for concurrent use of rh-IL-3, rh-GM-CSF and cytotoxic drugs whose purpose is to elevate remission rate during the phase of induced remission of leukemia.展开更多
Co-repressor N-CoR （nuclear receptor co-repressor） has important roles in different biological processes, including proliferation, differentiation and development. Mutant mice lacking N-CoR are embryonically lethal ...Co-repressor N-CoR （nuclear receptor co-repressor） has important roles in different biological processes, including proliferation, differentiation and development. Mutant mice lacking N-CoR are embryonically lethal and appear to die from anemia owing to defects in definitive erythropoiesis. However, the underlying molecular mechanisms of N-CoR- mediated erythroid differentiation are largely unknown. Using the human erythroleukemic K562 cell line, which can be chemically induced to differentiate into either erythroid or megakaryocytic lineages depending on the inducers used, we have investigated the role of N-CoR in erythroid differentiation. We show that knockdown of N-CoR either transiently （siRNA） or permanently （shRNA） impairs the cytosine arabinoside （Ara-C）- but not hemin-induced erythroid differ- entiation of K562 cells. RT-PCR analysis reveals that N-CoR is required for induction by Ara-C of 5-aminolevulinate synthase （ALA-S2）, a key enzyme involved in heme biosynthesis. Furthermore, the amount of N-CoR proteins increases significantly during Ara-C-induced K562 differentiation, apparently through a post-transcriptional mechanism. Consistent with the data from N-CoR-null mice, N-CoR is not required for the differentiation of K562 cells into megakaryocytic lineages, induced by phorbol 12-myristate 13-acetate. Thus, our in vitro study confirms a role for N-CoR in erythroid differentiation and reveals for the first time that N-CoR is required for the induction of a key enzyme involved in heme synthesis.展开更多
文摘Objective: To elucidate the pattern of chemo therapy drugs induced apoptosis and its role in chemo therapy of acute leukemia. Methods: Apoptosis induced by Ara C in human myeloid leukemia cell line HL 60 was investigated by applying light microscope, electron microscopy combined with DNA electrophoresis and flow cytometry analysis techniques. Results: Apoptosis per sisted throughout 36 h following addition of Ara C with a gradual augmentation. Efficiency of apoptosis was enhanced in a dosedependent pattern, HL 60 treated with six other chemotherapy drugs and peripheral white blood cells from a AML case undergoing DA regimen chemo therapy exhibited typical DNA ladder pattern. Further investigation indicated that chemotherapy drugs apop tosis came into being possibly by downregulating the expression of c myc and bcl 2 oncogenes. Conclusion: Chemotherapy induced apoptosis is the primary mecha nism of chemotherapy.
文摘The myeloid leukemic cell line HL-60 was studied by using DNA gel electrophoresis, flow cytomery, McAb C-myc, McAb Bc1-2 and CFU-L. From zero to 36 h,the apoptosis rates of 8 different phases and other indexes were observed. The results showed that with the prolonged time of drug incubation,apoptosis of HL-60 cells increased progressively. This effect can be enhanced obviously by rh-IL-3 and rh-GM-CSF. At the same time,the killed rate of leukemic cells by Ara-C induction was increased. C-myc expression was decreased and Bc1-2 expression did not display apparent change. Interestingly, the normal hemopoietic cells were not affected by these two kinds of cytokine. The theoretical basis was provided for concurrent use of rh-IL-3, rh-GM-CSF and cytotoxic drugs whose purpose is to elevate remission rate during the phase of induced remission of leukemia.
文摘Co-repressor N-CoR （nuclear receptor co-repressor） has important roles in different biological processes, including proliferation, differentiation and development. Mutant mice lacking N-CoR are embryonically lethal and appear to die from anemia owing to defects in definitive erythropoiesis. However, the underlying molecular mechanisms of N-CoR- mediated erythroid differentiation are largely unknown. Using the human erythroleukemic K562 cell line, which can be chemically induced to differentiate into either erythroid or megakaryocytic lineages depending on the inducers used, we have investigated the role of N-CoR in erythroid differentiation. We show that knockdown of N-CoR either transiently （siRNA） or permanently （shRNA） impairs the cytosine arabinoside （Ara-C）- but not hemin-induced erythroid differ- entiation of K562 cells. RT-PCR analysis reveals that N-CoR is required for induction by Ara-C of 5-aminolevulinate synthase （ALA-S2）, a key enzyme involved in heme biosynthesis. Furthermore, the amount of N-CoR proteins increases significantly during Ara-C-induced K562 differentiation, apparently through a post-transcriptional mechanism. Consistent with the data from N-CoR-null mice, N-CoR is not required for the differentiation of K562 cells into megakaryocytic lineages, induced by phorbol 12-myristate 13-acetate. Thus, our in vitro study confirms a role for N-CoR in erythroid differentiation and reveals for the first time that N-CoR is required for the induction of a key enzyme involved in heme synthesis.
