title: DAC can restore expression of NALP1 to suppress tumor growth in colon cancer.
abstract: Despite recent progress in the identification of genetic and molecular alternations in colorectal carcinoma, the precise molecular pathogenesis remains unclear. NALP1 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1) is a member of the nucleotide-binding oligomerization domain-like receptor family of proteins that are key organization proteins in the inflammasome. It is reported that NALP1 plays a central role in cell apoptosis, pyroptosis, inflammatory reactions and autoimmune diseases. DAC (5-aza-2-deoxycytidine) is an antitumor drug useful to lung cancer, myelodysplastic disorders, myelodysplasia and acute myeloid leukemia. In this study, we examined the expression of NALP1 in human normal and cancerous colon tissues using tissue microarray, western blot and quantitative real-time PCR and we measured the expression of NALP1 in three kinds of colon cancer cell lines and animal models before and after treatment with DAC. Furthermore, we examined the treatment effects of DAC on colon cancer in our animal model. Our data indicate that NALP1 is expressed low in human colorectal tumoral tissues relative to paratumoral tissues and was associated with the survival and tumor metastasis of patients. The expression of NALP1 increased after treatment with DAC both in vitro and in vivo. Furthermore, DAC suppressed the growth of colon cancer and increased lifespan in mouse model. Therefore, we conclude that NALP1 is expressed low in colon cancer and associated with the survival and tumor metastasis of patients, and treatment with DAC can restore NALP1 levels to suppress the growth of colon cancer.
authors.affiliation: 1] Department of Clinical Biochemistry, Dalian Medical University, Dalian 116044, China [2] Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Clinical Biochemistry, Dalian Medical University, Dalian 116044, China.
authors.forename: H
authors.initials: H
authors.lastname: Na
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: L
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: S
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Clinical Biochemistry, Dalian Medical University, Dalian 116044, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zuo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018899:CpG Islands / Q000235:genetics; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D000070576:NLR Proteins; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine