Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evide...Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. However, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry, The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner, Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.展开更多
In the present study, we aimed to assess the efficacy and safety of Homoharringtonine （HHT） for chronic myelogenous leukemia （CML）. Databases, such as PubMed, the Cochrane Library, EMbase, CENTRAL, VIP, WanFang Da...In the present study, we aimed to assess the efficacy and safety of Homoharringtonine （HHT） for chronic myelogenous leukemia （CML）. Databases, such as PubMed, the Cochrane Library, EMbase, CENTRAL, VIP, WanFang Data, CBM and CNKI, were electronically searched from inception to May 2014 for clinical trials on HHT for CML. Literatures were independently screened by two reviewers based on the inclusion and exclusion criteria, data were extracted, and methodological quality was assessed accordingly. Meta-analysis was performed using RevMan 5.2. Five trials were included consisting of a total of 423 patients. The results of meta-analysis showed that the HHT group was superior to the hydroxycarbamide （HU） group in terms of complete hematologic response rate （CHR）, major cytogenetic responses （MCyR） rate, partial cytogenetic responses （PCyR） rate, blast rate and 4-year survival rate. There was no statistical difference in complete cytogenetic response （CCyR） and minor cytogenetic response （mCyR） rates between the HHT group and HU group. HHT caused less adverse reaction. Therefore, HHT alone showed considerable short-term and long-term efficacy in the treatment of late-phase CML. It could be a good choice for some CML. Since moderate selection bias might exist in the methodological quality of the included studies which might affect the authenticity of outcomes, our conclusions should be further proved by conducting more high-quality, large-scale and double-blinded randomized controlled trials （RCTs）.展开更多
文摘Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. However, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry, The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner, Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.
文摘In the present study, we aimed to assess the efficacy and safety of Homoharringtonine （HHT） for chronic myelogenous leukemia （CML）. Databases, such as PubMed, the Cochrane Library, EMbase, CENTRAL, VIP, WanFang Data, CBM and CNKI, were electronically searched from inception to May 2014 for clinical trials on HHT for CML. Literatures were independently screened by two reviewers based on the inclusion and exclusion criteria, data were extracted, and methodological quality was assessed accordingly. Meta-analysis was performed using RevMan 5.2. Five trials were included consisting of a total of 423 patients. The results of meta-analysis showed that the HHT group was superior to the hydroxycarbamide （HU） group in terms of complete hematologic response rate （CHR）, major cytogenetic responses （MCyR） rate, partial cytogenetic responses （PCyR） rate, blast rate and 4-year survival rate. There was no statistical difference in complete cytogenetic response （CCyR） and minor cytogenetic response （mCyR） rates between the HHT group and HU group. HHT caused less adverse reaction. Therefore, HHT alone showed considerable short-term and long-term efficacy in the treatment of late-phase CML. It could be a good choice for some CML. Since moderate selection bias might exist in the methodological quality of the included studies which might affect the authenticity of outcomes, our conclusions should be further proved by conducting more high-quality, large-scale and double-blinded randomized controlled trials （RCTs）.
