This paper aims to investigate the effects of artesunate (ART) on growth and apoptosis in human osteosarcoma HOS cell line in vitro and in vivo and to explore the possible underlying mechanisms.Cell viability was meas...This paper aims to investigate the effects of artesunate (ART) on growth and apoptosis in human osteosarcoma HOS cell line in vitro and in vivo and to explore the possible underlying mechanisms.Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.The induction of apoptosis was detected by light and transmission electron microscopy and flow cytometry.Western blot analysis was used to investigate the related mechanisms.Nude mice were further employed to investigate the antitumour activity of ART in vivo.MTT assay results demonstrated that ART selectively inhibits the growth of HOS cells in a dose-and time-dependent manner.Based on the findings of light and transmission electron microscopy,Hoechst 33258 staining,and fluorescein isothiocyanate (FITC)-annexin V staining,the cytotoxicity of ART in HOS cells occurs through apoptosis.With ART treatment,cytosolic cytochrome c was increased,Bax expression was gradually upregulated,Bcl-2 expression was downregulated,and caspase-9 and caspase-3 were activated.Thus,the intrinsic apoptotic pathway may be involved in ART-induced apoptosis.Cell cycle analysis by flow cytometry indicated that ART may induce cell cycle arrest at G2 /M phase.In nude mice bearing HOS xenograft tumours,ART inhibited tumour growth and regulated the expressions of cleaved caspase-3 and survivin,in agreement with in vitro observations.ART has a selective antitumour activity against human osteosarcoma HOS cells,which may be related to its effects on induction of apoptosis via the intrinsic pathway.The results suggest that ART is a promising candidate for the treatment of osteosarcoma.展开更多
Objective To characterize and compare the different biological behaviors of two novel human osteosarcoma cell lines,Zos and Zos-M,established respectively from the primary site and the skip metastasis of an osteosarco...Objective To characterize and compare the different biological behaviors of two novel human osteosarcoma cell lines,Zos and Zos-M,established respectively from the primary site and the skip metastasis of an osteosarcoma patient.Methods Two展开更多
A number of solid tumors contain a distinct subpopulation of cells, termed cancer stem cells (CSCs) which represent the source for tissue renewal and hold malignant potential and which would be responsible for therapy...A number of solid tumors contain a distinct subpopulation of cells, termed cancer stem cells (CSCs) which represent the source for tissue renewal and hold malignant potential and which would be responsible for therapy resistance. Today, the winning goal in cancer research would be to find drugs to kill both cancer cells and cancer stem cells, while sparing normal cells. Osteosarcoma is an aggressive pediatric tumor of growing bones that, despite surgery and chemotherapy, is prone to relapse. We have recently selected from human osteosarcoma MG63 cells a cancer stem-like cell line (3AB-OS), which has unlimited proliferative potential, high levels of stemness-related markers, and in vivo tumorforming capacity in xenograft assays. Here, we have shown that 3AB-OS cells can differentiate in vitro into endoderm-, mesoderm-and ectoderm-derived lineages. Cell differentiation is morphological, molecular and functional. We propose that this model system of 3AB-OS differentiation in vitro might have a number of useful purposes, among which the study of molecular mechanisms of osteosarcoma origin, and the analysis of factors involved in specification of the various cell lineages. We still do not know either what are the shared and distinguishing characters between CSCs and normal stem cells, or what is the reason why the cancer stem cells, like the normal stem cells, have the ability to differentiate toward the derivatives of the primary germ layers. It is possible that each of the differentiation capability may be exploited by CSCs to supply their needs of growing and surviving in hostile microenvironment.展开更多
Human osteosarcoma MG-63 cells were induced into differentiation by 5 mmol/L hexamethylene bisacetamide （HMBA）. Their nuclear matrix proteins （NMPs） were selectively extracted and subjected to two-dimensional gel ...Human osteosarcoma MG-63 cells were induced into differentiation by 5 mmol/L hexamethylene bisacetamide （HMBA）. Their nuclear matrix proteins （NMPs） were selectively extracted and subjected to two-dimensional gel electrophoresis analysis. The results of protein patterns were analyzed by Melanie software. The spots of differentially expressed NMPs were excised and subjected to in situ digestion with trypsin. The maps of peptide mass fingerprinting were obtained by MALDI-TOF-MS analysis, and were submitted for NCBI database searches by Mascot tool. There were twelve spots changed remarkably during the differentiation induced by HMBA, nine of which were identified. The roles of the regulated proteins during the MG-63 differentiation were analyzed. This study suggests that the induced differentiation of cancer cells is accompanied by the changes of NMPs, and confirms the presence of some specific NMPs related to the cancer cell proliferation and differentiation. The changed NMPs are potential markers for cancer diagnosis or targets for cancer therapy.展开更多
文摘This paper aims to investigate the effects of artesunate (ART) on growth and apoptosis in human osteosarcoma HOS cell line in vitro and in vivo and to explore the possible underlying mechanisms.Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.The induction of apoptosis was detected by light and transmission electron microscopy and flow cytometry.Western blot analysis was used to investigate the related mechanisms.Nude mice were further employed to investigate the antitumour activity of ART in vivo.MTT assay results demonstrated that ART selectively inhibits the growth of HOS cells in a dose-and time-dependent manner.Based on the findings of light and transmission electron microscopy,Hoechst 33258 staining,and fluorescein isothiocyanate (FITC)-annexin V staining,the cytotoxicity of ART in HOS cells occurs through apoptosis.With ART treatment,cytosolic cytochrome c was increased,Bax expression was gradually upregulated,Bcl-2 expression was downregulated,and caspase-9 and caspase-3 were activated.Thus,the intrinsic apoptotic pathway may be involved in ART-induced apoptosis.Cell cycle analysis by flow cytometry indicated that ART may induce cell cycle arrest at G2 /M phase.In nude mice bearing HOS xenograft tumours,ART inhibited tumour growth and regulated the expressions of cleaved caspase-3 and survivin,in agreement with in vitro observations.ART has a selective antitumour activity against human osteosarcoma HOS cells,which may be related to its effects on induction of apoptosis via the intrinsic pathway.The results suggest that ART is a promising candidate for the treatment of osteosarcoma.
文摘Objective To characterize and compare the different biological behaviors of two novel human osteosarcoma cell lines,Zos and Zos-M,established respectively from the primary site and the skip metastasis of an osteosarcoma patient.Methods Two
文摘A number of solid tumors contain a distinct subpopulation of cells, termed cancer stem cells (CSCs) which represent the source for tissue renewal and hold malignant potential and which would be responsible for therapy resistance. Today, the winning goal in cancer research would be to find drugs to kill both cancer cells and cancer stem cells, while sparing normal cells. Osteosarcoma is an aggressive pediatric tumor of growing bones that, despite surgery and chemotherapy, is prone to relapse. We have recently selected from human osteosarcoma MG63 cells a cancer stem-like cell line (3AB-OS), which has unlimited proliferative potential, high levels of stemness-related markers, and in vivo tumorforming capacity in xenograft assays. Here, we have shown that 3AB-OS cells can differentiate in vitro into endoderm-, mesoderm-and ectoderm-derived lineages. Cell differentiation is morphological, molecular and functional. We propose that this model system of 3AB-OS differentiation in vitro might have a number of useful purposes, among which the study of molecular mechanisms of osteosarcoma origin, and the analysis of factors involved in specification of the various cell lineages. We still do not know either what are the shared and distinguishing characters between CSCs and normal stem cells, or what is the reason why the cancer stem cells, like the normal stem cells, have the ability to differentiate toward the derivatives of the primary germ layers. It is possible that each of the differentiation capability may be exploited by CSCs to supply their needs of growing and surviving in hostile microenvironment.
文摘Human osteosarcoma MG-63 cells were induced into differentiation by 5 mmol/L hexamethylene bisacetamide （HMBA）. Their nuclear matrix proteins （NMPs） were selectively extracted and subjected to two-dimensional gel electrophoresis analysis. The results of protein patterns were analyzed by Melanie software. The spots of differentially expressed NMPs were excised and subjected to in situ digestion with trypsin. The maps of peptide mass fingerprinting were obtained by MALDI-TOF-MS analysis, and were submitted for NCBI database searches by Mascot tool. There were twelve spots changed remarkably during the differentiation induced by HMBA, nine of which were identified. The roles of the regulated proteins during the MG-63 differentiation were analyzed. This study suggests that the induced differentiation of cancer cells is accompanied by the changes of NMPs, and confirms the presence of some specific NMPs related to the cancer cell proliferation and differentiation. The changed NMPs are potential markers for cancer diagnosis or targets for cancer therapy.
基金Supported by National Natural Science Foundation of China(30973127)Guangdong Provincial Bureau of Traditional Chinese Medicine Foundation(20142037)~~
