title: The in vitro and vivo anti-tumor effects and molecular mechanisms of suberoylanilide hydroxamic acid (SAHA) and MG132 on the aggressive phenotypes of gastric cancer cells.
abstract: Here, we found that both SAHA and MG132 synergistically inhibited proliferation, glycolysis and mitochondrial oxidization, induced cell cycle arrest and apoptosis in MGC-803 and MKN28 cells. SAHA increased cell migration and invasionat a low concentration. SAHA induced the overexpression of acetyl histone 3 and 4, which were recruited to p21, p27, Cyclin D1, c-myc and nanog promoters to transcriptionally up-regulate the former two and down-regulate the latter three. The expression of acetyl-histone 3 and 4 was increased during gastric carcinogenesis and positively correlated with cancer differentiation. SAHA and MG132 exposure suppressed tumor growth by inhibiting proliferation and inducing apoptosis in nude mice, increased serum ALT and AST levels and decreased hemaglobin level, white blood cell and neutrophil numbers. These data indicated that SAHA and MG132 in vivo and vitro synergistically induced cytotoxicity and apoptosis, suppressed proliferation, growth, migration and invasion of gastric cancer cells. Therefore, they might potentially be employed as chemotherapeutic agents if the hepatic injury and the killing effects of peripheral blood cells are avoided or ameliorated.
authors.affiliation: Cancer Center, The Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Lu
authors.affiliation: Cancer Center, The Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Cancer Center, The Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tian
authors.affiliation: Cancer Center, The Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Shou-Long
authors.initials: SL
authors.lastname: Tang
authors.affiliation: Department of Surgery, Panjin Central Hospital, Panjin, China.
authors.forename: Lian-Qian
authors.initials: LQ
authors.lastname: Li
authors.affiliation: Cancer Center, The Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Cancer Center, The Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.|Life Science Institute of Jinzhou Medical University, Jinzhou, China.
authors.forename: Hua-Chuan
authors.initials: HC
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009504:Neutrophils / Q000378:metabolism; D010101:Oxygen Consumption; D010641:Phenotype; D013274:Stomach Neoplasms / Q000188:drug therapy*; D000077337:Vorinostat; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007976:Leupeptins; D000077337:Vorinostat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: MG132; aggressive phenotypes; chemotherapy; gastric cancer; suberoylanilide hydroxamic acid