title: Rosiglitazone reverses mitomycin C resistance in human gastric cancer cells.
abstract: BACKGROUND
  To explore the mechanisms of rosiglitazone (ROS), a selective peroxisome proliferator-activated receptor gamma ligand, in reversing mitomycin C (MMC) resistance in a human drug-resistant gastric cancer cell line.
  
  
  METHODS
  The vincristine-resistant human gastric cancer cell line SGC7901/VCR and its parental cell line SGC7901 were treated with ROS, MMC (negative control), cyclosporine A+MMC (positive control) or ROS+MMC. A tetrazolium blue (methyl thiazolyl tetrazolium) assay was used to evaluate the sensitivity to these treatments. Flow cytometry analysis and acridine orange-ethidium bromide (AO-EB) fluorescent staining were used to determine the effects of ROS on MMC-induced apoptosis. Reverse transcription polymerase chain reaction and western blotting were used to measure the expression of multidrug resistant 1 (MDR1), Livin and P-glycoprotein (P-gp).
  
  
  RESULTS
  ROS administration dose dependently increased the reversal index in MMC-treated SCG7901/VCR cells. ROS increased apoptosis in SGC7901/VCR cells compared with the blank group and MMC group. ROS+MMC also increased apoptosis in SGC7901/VCR cells compared with other groups (P < 0.05 or P < 0.01). The mRNA expression of MDR1 and Livin and the protein expression of P-gp in SGC7901/VCR cells were significantly higher than those in SGC7901 cells (P < 0.01). However, ROS or ROS+MMC treatment markedly upregulated the mRNA expression of MDR1 and Livin and the protein expression of P-gp in SGC7901/VCR cells (P < 0.01).
  
  
  CONCLUSIONS
  ROS reverses MMC resistance in human gastric cancer SGC7901/VCR cells by reducing expression of MDR1, Livin and P-gp and increasing apoptosis.
authors: Department of Gastroenterology, The Second Affiliated Hospital, University of South China, Hengyang, Hunan, China.
authors: Li
authors: L
authors: Zhang
authors: Jian-Feng
authors: JF
authors: Hu
authors: Guo-Qing
authors: GQ
authors: Li
authors: Xiang
authors: X
authors: Xiao
authors: Qi
authors: Q
authors: Su
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D016685:Mitomycin / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077154:Rosiglitazone; D013274:Stomach Neoplasms / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; C419866:BIRC7 protein, human; D007004:Hypoglycemic Agents; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D016685:Mitomycin