Objective:To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As_2O_3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo,which may be a potential agen...Objective:To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As_2O_3-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-As_2O_3-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-As_2O_3-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-As_2O_3-stealth nanoparticles was then verified in a mouse model of Bel7402xenografts.Results:Anti-VEGFR-2 ScFv-As_2O_3-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 As_2O_3-stealth nanoparticles,anti-VEGFR-2 ScFv,and As203(61.4%,58.8%,20.5%,P<0.05).The concentration of As_2O_3 in anti-VEGFR-2 ScFv-As_2O_3-steallh nanoparticles group was more selectively.Conclusions:Anti-VEGFR-2 ScFv-As_2O_3-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
Objective:To study the effect of arsenic trioxide(As_2O_3)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(As_2O_3)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(As_2O_3)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,(As_2O_3),Rg3 and As_2O_3+Rg3 group.Transplantation tumor model of lung cancer in nude mice was constructed,followed by injection of certain concentrations of normal saline,As_2O_3,ginseng saponin Rg3 and As_2O_3+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,As_2O_3 group.Rg3 group and As_2O_3+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 As_2O_3 group.Rg3 groap and As_2O_3+Rg3 group was significantly higher than that of normal saline group(P<0.01);inhibition rate of tumor cells of As_2O_3+Rg3 group was significantly higher than that of the two groups given As_2O_3 or Rg3 alone(P<0.01).The tumor volume of As_2O_3 group,Rg3 group and As_2O_3+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,As_2O_3 group were significantly shorter than that of As_2O_3+Rg3 group(P<0.01);co-ordinated intervention ability of As_2O_3+Rg3 on NCI-H1299 cell was significantly higher than that of As_2O_3 or Rg3,separately.Conclusions:As_2O_3 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
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-As_2O_3-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-As_2O_3-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-As_2O_3-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-As_2O_3-stealth nanoparticles was then verified in a mouse model of Bel7402xenografts.Results:Anti-VEGFR-2 ScFv-As_2O_3-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 As_2O_3-stealth nanoparticles,anti-VEGFR-2 ScFv,and As203(61.4%,58.8%,20.5%,P<0.05).The concentration of As_2O_3 in anti-VEGFR-2 ScFv-As_2O_3-steallh nanoparticles group was more selectively.Conclusions:Anti-VEGFR-2 ScFv-As_2O_3-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.
基金supported by New Medical Technology Import Project in Henan Province,Number:2011020113
文摘Objective:To study the effect of arsenic trioxide(As_2O_3)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(As_2O_3)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,(As_2O_3),Rg3 and As_2O_3+Rg3 group.Transplantation tumor model of lung cancer in nude mice was constructed,followed by injection of certain concentrations of normal saline,As_2O_3,ginseng saponin Rg3 and As_2O_3+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,As_2O_3 group.Rg3 group and As_2O_3+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 As_2O_3 group.Rg3 groap and As_2O_3+Rg3 group was significantly higher than that of normal saline group(P<0.01);inhibition rate of tumor cells of As_2O_3+Rg3 group was significantly higher than that of the two groups given As_2O_3 or Rg3 alone(P<0.01).The tumor volume of As_2O_3 group,Rg3 group and As_2O_3+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,As_2O_3 group were significantly shorter than that of As_2O_3+Rg3 group(P<0.01);co-ordinated intervention ability of As_2O_3+Rg3 on NCI-H1299 cell was significantly higher than that of As_2O_3 or Rg3,separately.Conclusions:As_2O_3 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.
