ABSTRACT
PURPOSE: This study aimed to explore the mechanism of multi-drug resistance (MDR) in 5-fluorouracil (5-FU)-induced breast cancer cell MCF-7. METHODS: MCF-7 cells were exposed in stepwise escalating concentration of 5-FU to develop the resistant cell line, MCF-7/5-FU. Biological and molecular characteristics of the cells were studied through MTT, flow cytometry, real-time PCR, western-blot, and the global protein profiles between MCF-7/5-FU and parental MCF-7 were compared using proteomic approach. Then some of the differentially expressed proteins were validated by western-blot. In addition, the role of 14-3-3sigma was validated using gene transfection. RESULTS: Drug resistance of MCF-7/5-FU cells to 5-FU, MX, cDDP, ADM, TAXOL all increased significantly compared with MCF-7 cells and that maybe related to BCRP, but not MDR1 and MRP1. Differentially expressed proteins between MCF-7/5-FU and MCF-7 cells were identified; 12 proteins were up-regulated and 18 proteins were down-regulated in MCF-7/5-FU cells. Expressive levels of some proteins in western-blot validation were consistent with the results in proteomic analysis. Enforced 14-3-3sigma expression can increase the sensitivity of MCF-7/5-FU cells to 5-FU and cDDP. CONCLUSION: MDR of MCF-7/5-FU likely associated with differentially expressed proteins and 14-3-3sigma may play a positive role in chemotherapy. These findings may provide theoretical support for the prediction of chemotherapeutic response and reverse of MDR.
Subject(s)
Breast Neoplasms/drug therapy , Fluorouracil/pharmacology , Neoplasm Proteins/analysis , Proteomics/methods , 14-3-3 Proteins/physiology , Amino Acid Sequence , Biomarkers, Tumor/physiology , Breast Neoplasms/chemistry , Breast Neoplasms/pathology , Cell Line, Tumor , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Exonucleases/physiology , Exoribonucleases , Female , HSC70 Heat-Shock Proteins/physiology , Humans , Keratin-8/physiology , Molecular Sequence Data , Neoplasm Proteins/physiology , Peptide Elongation Factor Tu/physiology , Superoxide Dismutase/physiologyABSTRACT
OBJECTIVE: To investigate the protective effect of Dansheng injection on experimental rabbits' in spinal cord injury. METHODS: Thirty-two New Zealand rabbits were impacted between T12-T1 with a force of 150 g.cm-1 (10 g x 15 cm). The rabbits were randomly divided into the injury group, monitor group, L-NAME group and Dansheng group. The blood was obtained at 0 h, 4 h, 6 h to separate the serum at the end the injured spinal cord. Cord tissues were obtained for histological examination. Methyl-di-aldehyde (MDA), superoxide dismutase (SOD) and nitro oxide (NO) from the serum and spinal tissues homogenated were tested. RESULTS: MDA and NO increased in the injury group compared with the others, but SOD significantly decreased in the injury group compared with the others. Histological examination showed that neurons were degenerated and necrosed. The injury group displayed serious changes while the Dansheng group less changes. iNOS expressed in all the groups. CONCLUSION: Dansheng injection has some protective effect on spinal cord injury in the early stage.
