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Combining kallistatin gene therapy and meloxicam to treat hepatocellular carcinoma in mice

Hepatocellular carcinoma (HCC) is one of the most common cancer‐related causes of death, and conventional treatments offer unsatisfactory response. We have previously reported that kallistatin gene therapy suppressed the growth of HCC tumors by its anti‐angiogenic activity, and meloxicam, a selectiv... Full description

Journal Title: Cancer Science November 2009, Vol.100(11), pp.2226-2233
Main Author: Jiang, Xian
Other Authors: Li, Hali , Qiao, Haiquan , Jiang, Hongchi , Xu, Ruian , Sun, Xueying
Format: Electronic Article Electronic Article
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ID: ISSN: 1347-9032 ; E-ISSN: 1349-7006 ; DOI: 10.1111/j.1349-7006.2009.01306.x
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recordid: wj10.1111/j.1349-7006.2009.01306.x
title: Combining kallistatin gene therapy and meloxicam to treat hepatocellular carcinoma in mice
format: Article
creator:
  • Jiang, Xian
  • Li, Hali
  • Qiao, Haiquan
  • Jiang, Hongchi
  • Xu, Ruian
  • Sun, Xueying
subjects:
  • Vascular Endothelial Growth Factor -- Health Aspects
  • Surgical Clinics -- Health Aspects
  • House Mouse -- Health Aspects
  • Meloxicam -- Health Aspects
  • Hepatocellular Carcinoma -- Health Aspects
  • Cox-2 Inhibitors -- Health Aspects
  • Genetic Research -- Health Aspects
  • Fibroblast Growth Factors -- Health Aspects
  • Antigens -- Health Aspects
  • Endothelium -- Health Aspects
  • Gene Therapy -- Health Aspects
  • Cancer Treatment -- Health Aspects
  • Cancer Genetics -- Health Aspects
  • Liver Cancer -- Health Aspects
ispartof: Cancer Science, November 2009, Vol.100(11), pp.2226-2233
description: Hepatocellular carcinoma (HCC) is one of the most common cancer‐related causes of death, and conventional treatments offer unsatisfactory response. We have previously reported that kallistatin gene therapy suppressed the growth of HCC tumors by its anti‐angiogenic activity, and meloxicam, a selective COX‐2 inhibitor, inhibited proliferation and induced apoptosis of human HCC cells . The aim of this study was to determine whether combining kallistatin gene therapy and meloxicam could offer a better therapeutic effect to combat HCC in mice. A kallistatin expression plasmid was constructed and its expression was detected after intratumoral gene transfer. Both kallistatin gene therapy and meloxicam suppressed the growth of subcutaneous human HepG2 tumors established in BALB/c nude mice, and the combinational therapy showed a stronger effect in suppressing tumor growth, tumor angiogenesis and cell proliferation, and increasing cell apoptosis, than the respective monotherapies. Gene transfer of kallistatin inhibited tumor angiogenesis, and slightly inhibited cell proliferation and increased cell apoptosis , but had no effect on expression of vascular endothelial growth factor, basic fibroblast growth factor, proliferating cell nuclear antigen, Bcl‐2, Bax, or activation of caspase‐3. Meloxicam therapy inhibited cell proliferation, induced cell apoptosis, reduced expression of proliferating cell nuclear antigen, increased activation of caspase‐3, and upregulated Bax. Meloxicam also slightly inhibited tumor angiogenesis with no effect on the expression of vascular endothelial growth factor or basic fibroblast growth factor. Combining two novel anticancer agents, kallistatin targeting tumoral vascularization and meloxicam targeting cell proliferation and apoptosis, warrants investigation as a therapeutic strategy to combat HCC. ( 2009)
language:
source:
identifier: ISSN: 1347-9032 ; E-ISSN: 1349-7006 ; DOI: 10.1111/j.1349-7006.2009.01306.x
fulltext: fulltext
issn:
  • 1347-9032
  • 13479032
  • 1349-7006
  • 13497006
url: Link


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titleCombining kallistatin gene therapy and meloxicam to treat hepatocellular carcinoma in mice
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descriptionHepatocellular carcinoma (HCC) is one of the most common cancer‐related causes of death, and conventional treatments offer unsatisfactory response. We have previously reported that kallistatin gene therapy suppressed the growth of HCC tumors by its anti‐angiogenic activity, and meloxicam, a selective COX‐2 inhibitor, inhibited proliferation and induced apoptosis of human HCC cells . The aim of this study was to determine whether combining kallistatin gene therapy and meloxicam could offer a better therapeutic effect to combat HCC in mice. A kallistatin expression plasmid was constructed and its expression was detected after intratumoral gene transfer. Both kallistatin gene therapy and meloxicam suppressed the growth of subcutaneous human HepG2 tumors established in BALB/c nude mice, and the combinational therapy showed a stronger effect in suppressing tumor growth, tumor angiogenesis and cell proliferation, and increasing cell apoptosis, than the respective monotherapies. Gene transfer of kallistatin inhibited tumor angiogenesis, and slightly inhibited cell proliferation and increased cell apoptosis , but had no effect on expression of vascular endothelial growth factor, basic fibroblast growth factor, proliferating cell nuclear antigen, Bcl‐2, Bax, or activation of caspase‐3. Meloxicam therapy inhibited cell proliferation, induced cell apoptosis, reduced expression of proliferating cell nuclear antigen, increased activation of caspase‐3, and upregulated Bax. Meloxicam also slightly inhibited tumor angiogenesis with no effect on the expression of vascular endothelial growth factor or basic fibroblast growth factor. Combining two novel anticancer agents, kallistatin targeting tumoral vascularization and meloxicam targeting cell proliferation and apoptosis, warrants investigation as a therapeutic strategy to combat HCC. ( 2009)
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subjectVascular Endothelial Growth Factor -- Health Aspects ; Surgical Clinics -- Health Aspects ; House Mouse -- Health Aspects ; Meloxicam -- Health Aspects ; Hepatocellular Carcinoma -- Health Aspects ; Cox-2 Inhibitors -- Health Aspects ; Genetic Research -- Health Aspects ; Fibroblast Growth Factors -- Health Aspects ; Antigens -- Health Aspects ; Endothelium -- Health Aspects ; Gene Therapy -- Health Aspects ; Cancer Treatment -- Health Aspects ; Cancer Genetics -- Health Aspects ; Liver Cancer -- Health Aspects;
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abstractHepatocellular carcinoma (HCC) is one of the most common cancer‐related causes of death, and conventional treatments offer unsatisfactory response. We have previously reported that kallistatin gene therapy suppressed the growth of HCC tumors by its anti‐angiogenic activity, and meloxicam, a selective COX‐2 inhibitor, inhibited proliferation and induced apoptosis of human HCC cells . The aim of this study was to determine whether combining kallistatin gene therapy and meloxicam could offer a better therapeutic effect to combat HCC in mice. A kallistatin expression plasmid was constructed and its expression was detected after intratumoral gene transfer. Both kallistatin gene therapy and meloxicam suppressed the growth of subcutaneous human HepG2 tumors established in BALB/c nude mice, and the combinational therapy showed a stronger effect in suppressing tumor growth, tumor angiogenesis and cell proliferation, and increasing cell apoptosis, than the respective monotherapies. Gene transfer of kallistatin inhibited tumor angiogenesis, and slightly inhibited cell proliferation and increased cell apoptosis , but had no effect on expression of vascular endothelial growth factor, basic fibroblast growth factor, proliferating cell nuclear antigen, Bcl‐2, Bax, or activation of caspase‐3. Meloxicam therapy inhibited cell proliferation, induced cell apoptosis, reduced expression of proliferating cell nuclear antigen, increased activation of caspase‐3, and upregulated Bax. Meloxicam also slightly inhibited tumor angiogenesis with no effect on the expression of vascular endothelial growth factor or basic fibroblast growth factor. Combining two novel anticancer agents, kallistatin targeting tumoral vascularization and meloxicam targeting cell proliferation and apoptosis, warrants investigation as a therapeutic strategy to combat HCC. ( 2009)
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pubBlackwell Publishing Ltd
doi10.1111/j.1349-7006.2009.01306.x
pages2226-2233
date2009-11