Restoration of XAF1 expression induces apoptosis and inhibits tumor growth in gastric cancer
Copyright policy )Restoration of XAF1 expression induces apoptosis and inhibits tumor growth in gastric cancer
AbstractXAF1 (XIAP‐associated factor 1) is a novel XIAP binding protein that can antagonize XIAP and sensitize cells to other cell death triggers. Our previous results have shown that aberrant hypermethylation of the CpG sites in XAF1 promoter is strongly associated with lower expression of XAF1 in gastric cancers. In our study, we investigated the effect of restoration of XAF1 expression on growth of gastric cancers. We found that the restoration of XAF1 expression suppressed anchorage‐dependent and ‐independent growth and increased sensitivity to TRAIL and drug‐induced apoptosis. Stable cell clones expressing XAF1 exhibited delayed tumor initiation in nude mice. Restoration of XAF1 expression mediated by adenovirus vector greatly increased apoptosis in gastric cancer cell lines in a time‐ and dose‐dependent manner and sensitized cancer cells to TRAIL and drugs‐induced apoptosis. Adeno‐XAF1 transduction induced cell cycle G2/M arrest and upregulated the expression of p21 and downregulated the expression of cyclin B1 and cdc2. Notably, adeno‐XAF1 treatment significantly inhibited tumor growth, strongly enhanced the antitumor activity of TRAIL in a gastric cancer xenograft model in vivo, and significantly prolonged the survival time of animals bearing tumor xenografts. Complete eradication of established tumors was achieved on combined treatment with adeno‐XAF1 and TRAIL. Our results document that the restoration of XAF1 inhibits gastric tumorigenesis and tumor growth and that XAF1 is a promising candidate for cancer gene therapy. © 2009 UICC
- Chinese University of Hong Kong China (People's Republic of)
- University of Hong Kong China (People's Republic of)
- Children's Hospital of Eastern Ontario Canada
- Shanghai Jiao Tong University China (People's Republic of)
- University of Hong Kong (香港大學) China (People's Republic of)
Time Factors, TRAIL, Apoptosis, Mice, Mice, Inbred Balb C, Tnf-Related Apoptosis-Inducing Ligand - Metabolism - Pharmacology, Transduction, Genetic, Stomach Neoplasms - Genetics - Metabolism - Pathology - Physiopathology - Therapy, Antineoplastic Combined Chemotherapy Protocols, Adenovirus, Heterologous, Tumor, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Cell Cycle, XAF1, Cyclin-Dependent Kinase Inhibitor P21 - Metabolism, Drug Synergism, Cyclin B - Metabolism, Inbred Balb C, Up-Regulation, Gene Expression Regulation, Neoplastic, Intracellular Signaling Peptides And Proteins, Neoplasm Proteins - Metabolism - Pharmacology - Therapeutic Use, Disease Progression, Western, Plasmids, Cyclin-Dependent Kinase Inhibitor p21, Transplantation, Heterologous, Blotting, Western, Genetic Vectors, Down-Regulation, Cyclin B, Transfection, Cell Line, Adenoviridae, Cell cycle arrest, Transduction, Gene therapy, Antineoplastic Combined Chemotherapy Protocols - Pharmacology, Genetic, Cell Line, Tumor, In Situ Nick-End Labeling, Animals, Humans, Cyclin B1, Adaptor Proteins, Signal Transducing, Neoplastic, Transplantation, Animal, Genetic Therapy, Gene Therapy - Methods, Disease Models, Animal, Gene Expression Regulation, Disease Models, Tumorigenesis, Cell Cycle - Genetics, Gastric cancer, Apoptosis Regulatory Proteins
Time Factors, TRAIL, Apoptosis, Mice, Mice, Inbred Balb C, Tnf-Related Apoptosis-Inducing Ligand - Metabolism - Pharmacology, Transduction, Genetic, Stomach Neoplasms - Genetics - Metabolism - Pathology - Physiopathology - Therapy, Antineoplastic Combined Chemotherapy Protocols, Adenovirus, Heterologous, Tumor, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Cell Cycle, XAF1, Cyclin-Dependent Kinase Inhibitor P21 - Metabolism, Drug Synergism, Cyclin B - Metabolism, Inbred Balb C, Up-Regulation, Gene Expression Regulation, Neoplastic, Intracellular Signaling Peptides And Proteins, Neoplasm Proteins - Metabolism - Pharmacology - Therapeutic Use, Disease Progression, Western, Plasmids, Cyclin-Dependent Kinase Inhibitor p21, Transplantation, Heterologous, Blotting, Western, Genetic Vectors, Down-Regulation, Cyclin B, Transfection, Cell Line, Adenoviridae, Cell cycle arrest, Transduction, Gene therapy, Antineoplastic Combined Chemotherapy Protocols - Pharmacology, Genetic, Cell Line, Tumor, In Situ Nick-End Labeling, Animals, Humans, Cyclin B1, Adaptor Proteins, Signal Transducing, Neoplastic, Transplantation, Animal, Genetic Therapy, Gene Therapy - Methods, Disease Models, Animal, Gene Expression Regulation, Disease Models, Tumorigenesis, Cell Cycle - Genetics, Gastric cancer, Apoptosis Regulatory Proteins
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).39 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!