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
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
Background P-glycoprotein （P-gp） encoded by ATP-binding cassette sub-family B member 1 （ABCB1） gene is a kind of ATP-dependent drug transporter, which plays important roles in multidrug resistance （MDR） of human...Background P-glycoprotein （P-gp） encoded by ATP-binding cassette sub-family B member 1 （ABCB1） gene is a kind of ATP-dependent drug transporter, which plays important roles in multidrug resistance （MDR） of human cancers, such as osteosarcoma. Curcumin is a natural phenolic coloring compound originating from the rhizomes of Curcuma Ionga, which is proved to possess antitumor biological activities including reversion of MDR. However, the effect and molecular mechanisms of curcumin to osteosarcoma MDR remain unclear.展开更多
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
目的探讨人参皂苷Rg_(3)对过氧化氢诱导的人晶状体上皮细胞氧化损伤的改善作用及对核转录因子E2相关因子2(nuclear factor E2 related factor 2,Nrf2)/血红素加氧酶-1(heme oxygenase 1,HO-1)信号通路的调节作用。方法用不同浓度人参皂...目的探讨人参皂苷Rg_(3)对过氧化氢诱导的人晶状体上皮细胞氧化损伤的改善作用及对核转录因子E2相关因子2(nuclear factor E2 related factor 2,Nrf2)/血红素加氧酶-1(heme oxygenase 1,HO-1)信号通路的调节作用。方法用不同浓度人参皂苷Rg_(3)处理过氧化氢诱导的SRA01/04细胞,用噻唑盐(methyl thiazolyl tetrazolium,MTT)法检测细胞存活率。将第3代对数生长期SRA01/04细胞随机分为正常组、氧化损伤组(用200μmol∙mL^(−1)过氧化氢处理)、人参皂苷Rg_(3)低剂量组和人参皂苷Rg_(3)高剂量组(分别用40、80μg∙mL^(−1)人参皂苷Rg_(3)处理6 h,更换培养基后用200μmol∙mL^(−1)过氧化氢处理12 h),用MTT法检测细胞存活率,用流式细胞仪检测细胞凋亡率,用试剂盒检测丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxidedismutase,SOD)和谷胱甘肽过氧化物酶(glutathioneperoxidase,GSH-Px)的含量,用蛋白印迹法检测Nrf2、Kelch样环氧氯丙烷相关蛋白1(Kelch like epichlorohydrin related protein 1,Keap1)和HO-1蛋白的相对表达量。结果与0μg∙mL^(−1)人参皂苷Rg_(3)组比较,10、20、40、80μg∙mL^(−1)人参皂苷Rg_(3)组的细胞存活率逐渐升高(P<0.05)。与正常组比较,氧化损伤组的细胞存活率、SOD和GSHPx含量以及Nrf2、Keap1和HO-1蛋白相对表达量降低,细胞凋亡率和MDA含量升高(P<0.05);与氧化损伤组比较,人参皂苷Rg_(3)低剂量和人参皂苷Rg_(3)高剂量组的细胞存活率、SOD和GSH-Px含量以及Nrf2、Keap1和HO-1蛋白的相对表达量升高,细胞凋亡率和MDA含量降低(P<0.05);人参皂苷Rg_(3)低剂量和人参皂苷Rg_(3)高剂量组各项指标水平变化规律相同,人参皂苷Rg_(3)高剂量组更显著(P<0.05)。结论人参皂苷Rg_(3)可抑制过氧化氢诱导的人晶状体上皮细胞凋亡,减轻氧化应激损伤,其可能是通过激活Nrf2/HO-1信号通路发挥调节作用的。展开更多
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Background P-glycoprotein （P-gp） encoded by ATP-binding cassette sub-family B member 1 （ABCB1） gene is a kind of ATP-dependent drug transporter, which plays important roles in multidrug resistance （MDR） of human cancers, such as osteosarcoma. Curcumin is a natural phenolic coloring compound originating from the rhizomes of Curcuma Ionga, which is proved to possess antitumor biological activities including reversion of MDR. However, the effect and molecular mechanisms of curcumin to osteosarcoma MDR remain unclear.
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.
文摘目的探讨人参皂苷Rg_(3)对过氧化氢诱导的人晶状体上皮细胞氧化损伤的改善作用及对核转录因子E2相关因子2(nuclear factor E2 related factor 2,Nrf2)/血红素加氧酶-1(heme oxygenase 1,HO-1)信号通路的调节作用。方法用不同浓度人参皂苷Rg_(3)处理过氧化氢诱导的SRA01/04细胞,用噻唑盐(methyl thiazolyl tetrazolium,MTT)法检测细胞存活率。将第3代对数生长期SRA01/04细胞随机分为正常组、氧化损伤组(用200μmol∙mL^(−1)过氧化氢处理)、人参皂苷Rg_(3)低剂量组和人参皂苷Rg_(3)高剂量组(分别用40、80μg∙mL^(−1)人参皂苷Rg_(3)处理6 h,更换培养基后用200μmol∙mL^(−1)过氧化氢处理12 h),用MTT法检测细胞存活率,用流式细胞仪检测细胞凋亡率,用试剂盒检测丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxidedismutase,SOD)和谷胱甘肽过氧化物酶(glutathioneperoxidase,GSH-Px)的含量,用蛋白印迹法检测Nrf2、Kelch样环氧氯丙烷相关蛋白1(Kelch like epichlorohydrin related protein 1,Keap1)和HO-1蛋白的相对表达量。结果与0μg∙mL^(−1)人参皂苷Rg_(3)组比较,10、20、40、80μg∙mL^(−1)人参皂苷Rg_(3)组的细胞存活率逐渐升高(P<0.05)。与正常组比较,氧化损伤组的细胞存活率、SOD和GSHPx含量以及Nrf2、Keap1和HO-1蛋白相对表达量降低,细胞凋亡率和MDA含量升高(P<0.05);与氧化损伤组比较,人参皂苷Rg_(3)低剂量和人参皂苷Rg_(3)高剂量组的细胞存活率、SOD和GSH-Px含量以及Nrf2、Keap1和HO-1蛋白的相对表达量升高,细胞凋亡率和MDA含量降低(P<0.05);人参皂苷Rg_(3)低剂量和人参皂苷Rg_(3)高剂量组各项指标水平变化规律相同,人参皂苷Rg_(3)高剂量组更显著(P<0.05)。结论人参皂苷Rg_(3)可抑制过氧化氢诱导的人晶状体上皮细胞凋亡,减轻氧化应激损伤,其可能是通过激活Nrf2/HO-1信号通路发挥调节作用的。
