Objective:To study the effect of arsenic trioxide（As2O3）combined with ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma.Methods:MTT method was used to measu...Objective:To study the effect of arsenic trioxide（As2O3）combined with ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma.Methods:MTT method was used to measure the inhibition effect of（As2O3）combined Rg3 on NC1-H1299 cells,and the proliferation inhibiting effect was observed via establishing the transplanted tumor model in vitro.A total of 40 tumor-bearing nude mice were randomly divided into normal saline group,（As2O3）,Rg3 and As2O3+Rg3 group.Transplantation tumor model of lung cancer in nude mice was constructed,followed by injection of certain concentrations of normal saline,As2O3,ginseng saponin Rg3 and As2O3+Rg3 every day.The survival duration and the tumors size of the mice were recorded and the Kaplan-Meier curve was made;microscopic observation of apoptosis of tumor cells in vivo was done using TUNEL staining.Results:After 72 h of injection.inhibition rate of tumor cell in normal saline group,As2O3 group.Rg3 group and As2O3+Rg3 group was（5.66±0.31）%,（65.58±4.75）%,（44.69±3.32）%and（82.67±5.43）%,respectively.Inhibition rate of tumor cell in As2O3 group.Rg3 groap and As2O3+Rg3 group was significantly higher than that of normal saline group（P【0.01）;inhibition rate of tumor cells of As2O3+Rg3 group was significantly higher than that of the two groups given As2O3 or Rg3 alone（P【0.01）.The tumor volume of As2O3 group,Rg3 group and As2O3+Rg3 group shrank to（65.38±3.25）%,（77.68±3.43）%and（42.65±3.55）%of the original,tumor volume of saline group was 1.21 times of the original size（P【0.01）;Median survival of saline group,Rg3 group,As2O3 group were significantly shorter than that of As2O3+Rg3 group（P【0.01）;co-ordinated intervention ability of As2O3+Rg3 on NCI-H1299 cell was significantly higher than that of As2O3 or Rg3,separately.Conclusions:As2O3 combined with Rg3 can significantly inhibit prolifaration of NCI-H1299 cells in lung cancer,prolong survival fo tumor-bearing nude mice,and promote tumor cell apoptosis,and have significant effect on lung cancer treatment.展开更多
Objective:To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo,which may be a potential agents...Objective:To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo,which may be a potential agents with sensitivity and targeting ability for human hepatocellular cancer.Methods:Humanized anli-VECFR-2 ScFv-As2O3-stealth nanoparticles conjugate was previously constructed using ribosome display technology and antibody conjugate technology.In this combined in vitro and in vivo study,the inhibitory effects of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on tumor growth,invasion,and metastasis was observed with human liver carcinoma cell line Bel7402 and normal cell L02 by MTT assay,Tanswell assay,Hochest33258 staining,and DNA ladder analysis.The anticancer activity and distribution of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles was then verified in a mouse model of Bel7402xenografts.Results:Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly inhibited the proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yh-2,5-diphenyltetrazolium bromide assay while had almost no effects on L02 cells.And the apoptosis inducing effects were proved by Hochest33258 staining and DNA ladder analysis.Transwell assay found that the drug also inhibited the metastasis ability of tumor cells.Furthermore,anti-VEGFR-2 ScFv-As^-stealth nanoparticles significantly delayed the growth of Bel7402 xenografts after administration（92.9%）,followed by As2O3-stealth nanoparticles,anti-VEGFR-2 ScFv,and As203（61.4%,58.8%,20.5%,P【0.05）.The concentration of As2O3 in anti-VEGFR-2 ScFv-As2O3-steallh nanoparticles group was more selectively.Conclusions:Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles is a potent and selective anti-hepatocellular carcinoma agent which could inhibit the growth of liver cancer as a targeting agent both in vitro and in vivo and also significantly inhibit angiogenesis.展开更多
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.
Sphingosine kinase 1(SphK1)is an important synthetase during the synthesis of sphingosine-1-phosphate(S1P)from sphingosine(Sph).Previous studies demonstrated that arsenic trioxide(As_(2)O_(3))could reduce the level of...Sphingosine kinase 1(SphK1)is an important synthetase during the synthesis of sphingosine-1-phosphate(S1P)from sphingosine(Sph).Previous studies demonstrated that arsenic trioxide(As_(2)O_(3))could reduce the level of S1P in human gastric cancer cell line MGC-803,indicating that As_(2)O_(3) may inhibit the activity of SphK1.In this study,the effect of As_(2)O_(3) on the SphK1 activation pathway was investigated.Western blot and quantitative real-time PCR analysis were used to evaluate the changes in protein and mRNA levels.The multi-dimensional mass spectrometry-based shotgun lipidomics method(MDMS-SL)was used for the quantitative detection of phosphatidylserine(PS)and phosphatidic acid(PA).The results revealed that As_(2)O_(3) did not affect the protein and mRNA expression of SphK1 in the MGC-803 cells.However,As_(2)O_(3) increased the levels of p-ERK1/2 and CIB1 in the SphK1 activation pathway and decreased the levels of PS and PA in the MGC-803 cells.The outcomes suggested that As_(2)O_(3) may enhance the activity of SphK1 by increasing the levels of p-ERK1/2 and CIB1 and decrease the activity of SphK1 by decreasing the levels of PS and PA.It was suggested that the inhibition effect is stronger and resulting in an overall decrease in the activity of SphK1.展开更多
观察不同剂量As_(2)O_(3)联合^(125)I粒子植入对肺癌移植瘤小鼠的抑瘤作用和安全性。构建肺癌异种移植瘤小鼠模型,当肿瘤体积达到约300 mm 3时,将小鼠随机分为6组,连续治疗15 d。测量小鼠肿瘤瘤径、体重、饮食,检测小鼠血清ALT、AST、LD...观察不同剂量As_(2)O_(3)联合^(125)I粒子植入对肺癌移植瘤小鼠的抑瘤作用和安全性。构建肺癌异种移植瘤小鼠模型,当肿瘤体积达到约300 mm 3时,将小鼠随机分为6组,连续治疗15 d。测量小鼠肿瘤瘤径、体重、饮食,检测小鼠血清ALT、AST、LDH、CK、BUN、Cr浓度及脏器指数,HE染色评估主要脏器组织病理学变化。结果显示:与模型组相比,单用As_(2)O_(3)以及As_(2)O_(3)联合^(125)I粒子植入使小鼠饮食量和体重减少;单用As_(2)O_(3)(2.5 mg/kg、5 mg/kg)、^(125)I粒子(0.7 mci)治疗组以及联合治疗组均能明显抑制小鼠肿瘤生长(P<0.05);联合治疗组抑制作用优于单用As_(2)O_(3)和^(125)I粒子植入组(P<0.001);联合治疗组对小鼠血清生化功能及脏器指数无明显影响(P>0.05),组织病理学观察未见明显异常。综上,As_(2)O_(3)联合^(125)I粒子植入能够抑制肺癌移植瘤小鼠肿瘤生长,且优于单用As_(2)O_(3)和^(125)I粒子植入,方法安全可行。展开更多
基金supported by New Medical Technology Import Project in Henan Province,Number:2011020113
文摘Objective:To study the effect of arsenic trioxide（As2O3）combined with ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma.Methods:MTT method was used to measure the inhibition effect of（As2O3）combined Rg3 on NC1-H1299 cells,and the proliferation inhibiting effect was observed via establishing the transplanted tumor model in vitro.A total of 40 tumor-bearing nude mice were randomly divided into normal saline group,（As2O3）,Rg3 and As2O3+Rg3 group.Transplantation tumor model of lung cancer in nude mice was constructed,followed by injection of certain concentrations of normal saline,As2O3,ginseng saponin Rg3 and As2O3+Rg3 every day.The survival duration and the tumors size of the mice were recorded and the Kaplan-Meier curve was made;microscopic observation of apoptosis of tumor cells in vivo was done using TUNEL staining.Results:After 72 h of injection.inhibition rate of tumor cell in normal saline group,As2O3 group.Rg3 group and As2O3+Rg3 group was（5.66±0.31）%,（65.58±4.75）%,（44.69±3.32）%and（82.67±5.43）%,respectively.Inhibition rate of tumor cell in As2O3 group.Rg3 groap and As2O3+Rg3 group was significantly higher than that of normal saline group（P【0.01）;inhibition rate of tumor cells of As2O3+Rg3 group was significantly higher than that of the two groups given As2O3 or Rg3 alone（P【0.01）.The tumor volume of As2O3 group,Rg3 group and As2O3+Rg3 group shrank to（65.38±3.25）%,（77.68±3.43）%and（42.65±3.55）%of the original,tumor volume of saline group was 1.21 times of the original size（P【0.01）;Median survival of saline group,Rg3 group,As2O3 group were significantly shorter than that of As2O3+Rg3 group（P【0.01）;co-ordinated intervention ability of As2O3+Rg3 on NCI-H1299 cell was significantly higher than that of As2O3 or Rg3,separately.Conclusions:As2O3 combined with Rg3 can significantly inhibit prolifaration of NCI-H1299 cells in lung cancer,prolong survival fo tumor-bearing nude mice,and promote tumor cell apoptosis,and have significant effect on lung cancer treatment.
基金supported by Natural Science Foundation of China(81060187)the Natural Science Foundation of Jiangxi Province(2008GQY0050)
文摘Objective:To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo,which may be a potential agents with sensitivity and targeting ability for human hepatocellular cancer.Methods:Humanized anli-VECFR-2 ScFv-As2O3-stealth nanoparticles conjugate was previously constructed using ribosome display technology and antibody conjugate technology.In this combined in vitro and in vivo study,the inhibitory effects of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on tumor growth,invasion,and metastasis was observed with human liver carcinoma cell line Bel7402 and normal cell L02 by MTT assay,Tanswell assay,Hochest33258 staining,and DNA ladder analysis.The anticancer activity and distribution of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles was then verified in a mouse model of Bel7402xenografts.Results:Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly inhibited the proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yh-2,5-diphenyltetrazolium bromide assay while had almost no effects on L02 cells.And the apoptosis inducing effects were proved by Hochest33258 staining and DNA ladder analysis.Transwell assay found that the drug also inhibited the metastasis ability of tumor cells.Furthermore,anti-VEGFR-2 ScFv-As^-stealth nanoparticles significantly delayed the growth of Bel7402 xenografts after administration（92.9%）,followed by As2O3-stealth nanoparticles,anti-VEGFR-2 ScFv,and As203（61.4%,58.8%,20.5%,P【0.05）.The concentration of As2O3 in anti-VEGFR-2 ScFv-As2O3-steallh nanoparticles group was more selectively.Conclusions:Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles is a potent and selective anti-hepatocellular carcinoma agent which could inhibit the growth of liver cancer as a targeting agent both in vitro and in vivo and also significantly inhibit angiogenesis.
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This work was funded by the Natural Science Foundation of the Zhejiang Province,Grant No.LY17H280006the National Natural Science Foundation of China,Grant No.81803776.
文摘Sphingosine kinase 1(SphK1)is an important synthetase during the synthesis of sphingosine-1-phosphate(S1P)from sphingosine(Sph).Previous studies demonstrated that arsenic trioxide(As_(2)O_(3))could reduce the level of S1P in human gastric cancer cell line MGC-803,indicating that As_(2)O_(3) may inhibit the activity of SphK1.In this study,the effect of As_(2)O_(3) on the SphK1 activation pathway was investigated.Western blot and quantitative real-time PCR analysis were used to evaluate the changes in protein and mRNA levels.The multi-dimensional mass spectrometry-based shotgun lipidomics method(MDMS-SL)was used for the quantitative detection of phosphatidylserine(PS)and phosphatidic acid(PA).The results revealed that As_(2)O_(3) did not affect the protein and mRNA expression of SphK1 in the MGC-803 cells.However,As_(2)O_(3) increased the levels of p-ERK1/2 and CIB1 in the SphK1 activation pathway and decreased the levels of PS and PA in the MGC-803 cells.The outcomes suggested that As_(2)O_(3) may enhance the activity of SphK1 by increasing the levels of p-ERK1/2 and CIB1 and decrease the activity of SphK1 by decreasing the levels of PS and PA.It was suggested that the inhibition effect is stronger and resulting in an overall decrease in the activity of SphK1.
