期刊
AMERICAN JOURNAL OF THE MEDICAL SCIENCES
卷 343, 期 5, 页码 382-387出版社
ELSEVIER SCIENCE INC
DOI: 10.1097/MAJ.0b013e31822f3c63
关键词
PPAR gamma; ROS; Multidrug resistance; SGC7901/VCR cell line
资金
- Foundation of Natural Science of Hunan Province [08JJ5002]
- Foundation of Science and Technology of Hunan Province [2009SK3138]
- Scientific Research Foundation from Health Department of Hunan Province [2007110]
Introduction: 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.
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