Liver-specific gene therapy of hepatocellular carcinoma by targeting human telomerase reverse transcriptase with pegylated immuno-lipopolyplexes

Hu, Yurong; Shen, Yingying; Ji, Baofang; Yin, Shasha; Ren, Xueling; Chen, Tingting; Ma, Yue; Zhang, Zhenzhong; Zhang, Yun

doi:10.1016/j.ejpb.2010.12.036

Cited by 8 publications

(3 citation statements)

References 23 publications

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“…Fluorescent microscopy was performed to visualize GFP expression. Transfection efficiency was calculated as percentage of cells expressing GFP by counting the number of the cells that display or do not display GFP signals in five areas (the upper left, the upper right, the bottom left, the bottom right, and the center) under four randomly chosen microscopic visions 49 .…”

Section: Methodsmentioning

confidence: 99%

Asialoglycoprotein receptor-magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma

Xue

Feng

Wang

et al. 2016

Sci Rep

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We developed a nanovector with double targeting properties for efficiently delivering the tumor suppressor gene RASSF1A specifically into hepatocellular carcinoma (HCC) cells by preparing galactosylated-carboxymethyl chitosan-magnetic iron oxide nanoparticles (Gal-CMCS-Fe3O4-NPs). After conjugating galactose and CMCS to the surface of Fe3O4-NPs, we observed that Gal-CMCS-Fe3O4-NPs were round with a relatively stable zeta potential of +6.5 mV and an mean hydrodynamic size of 40.1 ± 5.3 nm. Gal-CMCS-Fe3O4-NPs had strong DNA condensing power in pH 7 solution and were largely nontoxic. In vitro experiments demonstrated that Gal-CMCS-Fe3O4-NPs were highly selective for HCC cells and liver cells. In vivo experiments showed the specific accumulation of Gal-CMCS-Fe3O4-NPs in HCC tissue, especially with the aid of an external magnetic field. Nude mice with orthotopically transplanted HCC received an intravenous injection of the Gal-CMCS-Fe3O4-NPs/pcDNA3.1(+)RASSF1A compound and intraperitoneal injection of mitomycin and had an external magnetic field applied to the tumor area. These mice had the smallest tumors, largest percentage of TUNEL-positive cells, and highest caspase-3 expression levels in tumor tissue compared to other groups of treated mice. These results suggest the potential application of Gal-CMCS-Fe3O4-NPs for RASSF1A gene delivery for the treatment of HCC.

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Section: Methodsmentioning

confidence: 99%

Asialoglycoprotein receptor-magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma

Xue

Feng

Wang

et al. 2016

Sci Rep

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“…The present study and Ming's study showed the similar potential effects of combined β-escin and 5-FU to reduce Bcl-2 protein expression, cell proliferation, and inducing cell apoptosis in SMMC-7721 and MCF7 cells with respect to untreated control cells or single treatment of 5-FU and β-escin. SMMC-7721 and MCF7 have different tissue origin; however, they have some similar properties such as positive telomerase activity[2930] which may be influenced in their response to the effects of combined β-escin and 5-FU. [31] It seems that the combination of β-escin and 5-FU may be effective, at least partly, on other cancer cell lines in special ratio and concentration.…”

Section: Discussionmentioning

confidence: 99%

Activation of p53 gene expression and synergistic antiproliferative effects of 5-fluorouracil and β-escin on MCF7 cells

Mazrouei

Raeisi

Lemoigne³

et al. 2019

J Med Signals Sens

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One of the most common malignancies in women is breast cancer. β-escin has pharmacological anticancer effects. 5-fluorouracil (5-FU) has antimetabolite and antiproliferative properties. The purpose of this study was to investigate the combined effects of 5-FU and β-escin on apoptosis, colony formation, Bcl-2 signaling protein, and p53 gene expression in MCF7 breast cancer cell line. The cytotoxic effects, the number of colonies, apoptosis, p53 gene expression, and Bcl-2 signaling protein of the combined 5-FU and β-escin on MCF7 cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, clonogenic assay, flow cytometry, real-time quantitative polymerase chain reaction, and western blotting methods, respectively. Half-maximal inhibitory concentration values of β-escin and 5-FU were 80 μg/ml and 2 μM, respectively. The combination of 5-FU and β-escin on MCF7 cell viability showed a combination index equal to 0.5. The expression of p53 and apoptosis increased in the combination of 5-FU and β-escin on MCF7 cells compared to that of control group (P < 0.05). In addition, the number of colonies and Bcl-2 signaling protein in combination of 5-FU and β-escin decreased with respect to untreated control cells or single treatment of 5-FU and β-escin. The combination of 5-FU and β-escin not only has synergistic effects by increasing cell apoptosis and p53 gene expression but also decreases Bcl-2 signaling protein in MCF7 cell lines.

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“…These observations indicate that utilization of AFP promoter and enhancer driven expression in a plasmid vector can confer the selective expression of a heterologous suicide gene in HCC cells. Therefore, it may be feasible to produce a high local concentration of AGAP at the tumor site by targeting the drug in a tumor cell-specific manner, subsequently resulting in the targeted killing of cancer cells ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Cell-specific expression of the analgesic-antitumor peptide coding sequence under the control of the human α-fetoprotein gene promoter and enhancer

Jin

Lin

Guan

et al. 2015

Experimental and Therapeutic Medicine

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The aim of the present study was to construct a gene-modified hepatocellular carcinoma (HCC)-specific analgesic-antitumor peptide (AGAP) expression vector regulated by the α-fetoprotein (AFP) promoter and enhancer, in order to evaluate its effect. The AFP promoter is generally used in HCC-specific gene therapy strategies. However, this approach is limited by the weak activity of the AFP promoter. Linking the AFP enhancer and promoter has been shown to generate a stronger and more HCC-selective promoter. The AGAP DNA fragment was amplified from the total RNA of the Chinese scorpion, Buthus martensii Karsch. The fragment was subsequently cloned into the pAFP plasmid with the minimal essential DNA fragment, which included the AFP gene promoter and enhancer, to construct the recombinant plasmid, pAFP-AGAP. The plasmid was transfected into HepG2 cells and the mRNA expression levels of AGAP were detected by reverse transcription polymerase chain reaction (RT-PCR). In addition, Cell Counting Kit 8 (CCK-8) was used to analyze the cytotoxicity of plasmid transfection. The length, position and orientation of the inserted AGAP gene were all confirmed to be correct; thus, the recombinant vector was successfully constructed. Using RT-PCR and CCK-8 analysis, the mRNA expression levels of AGAP and the cytotoxicity in AFP-producing human HCC cells were determined. The AFP promoter and enhancer were found to specifically accelerate the expression of the target genes within the cells that were positive for AFP. Therefore, the method used in the present study was demonstrated to be a novel integration of traditional Chinese medicine with western medicine.

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Liver-specific gene therapy of hepatocellular carcinoma by targeting human telomerase reverse transcriptase with pegylated immuno-lipopolyplexes

Cited by 8 publications

References 23 publications

Asialoglycoprotein receptor-magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma

Asialoglycoprotein receptor-magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma

Activation of p53 gene expression and synergistic antiproliferative effects of 5-fluorouracil and β-escin on MCF7 cells

Cell-specific expression of the analgesic-antitumor peptide coding sequence under the control of the human α-fetoprotein gene promoter and enhancer

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