| The incidence of breast cancer is the highest in female malignant tumor diseases’incidences. And there is a rising trend. After operation, chemotherapy and othercomprehensive treatment, early breast cancer gets good therapeutic results, whileadvanced breast cancer loses the chance of operation and has to receive chemotherapy.At present, chemotherapy with anthracycline and taxane is the best choice foradvanced breast cancer. Although the effect is significant, there is still20%~30%patients who have drug resistance. In the treatments of advanced breast cancer, thefollow-up treatments for drug resistant patients is a difficult problem for the currentclinical science. As the third generation chemotherapy drugs such as gemcitabine,capecitabine and vinorelbine appear, the effect of chemotherapy for advanced breastcancer has increased. How to improve the efficienty of chemotherapy has become oneof the most urgent problems. The present study is focusing on the selection of themost appropriate treatment according to the different individual characteristics ofpatients, called the individual treatment. The individual treatment not only canimprove the efficacy of chemotherapy in a certain extent, but also avoid using invaliddrug which would bring physical and economic loss of patients. In recent years, withthe development of molecular pharmacology and molecular biology, people have afurther understanding of the mechanism of tumor drug resistance, the differentindividual response to drug treatment and prognosis which is leaded by abnormalgene expression. Thus people realize it soberly that is the basis and conditions forindividualized treatment in cancer.Objective：To investigate the changes of CN-Ⅱ and APE/Ref-1expression inhuman breast cancer cell line MCF-7after induction of gemcitabine and to study the effects of gemcitabine on chemoresistance in breast cancer.Method：After human breast cancer cell line MCF-7was incubated withdifferent concentration of gemcitabine for24h, the mRNA and protein levels ofcytosolic5’-nucleotidase Ⅱ (CN-Ⅱ) and apurinic/apyrimidinic endonuclease/redoxfactor-1(APE/Ref-1) were determined by reverse transcription-polymerase chainreaction (RT-PCR) and Western blot, respectively. After human breast cancer cell lineMCF-7was incubated with50nmol/L concentration of gemcitabine for0,3,7,10,13and16days, the apoptosis ratio was determinated by flow cytometry, and the mRNAand protein levels of CN-Ⅱ and APE/Ref-1of surival cells were determined by reversetranscription-polymerase chain reaction (RT-PCR) and Western blot, respectively.Results：Twenty-four hours after treatment with gemcitabine．the expression ofCN-Ⅱ and APE/Ref-1in human breast cancer cell line MCF-7were elevatedsignificantly both at mRNA and protein levels，and were positively correlated withgemcitabine concentration. After human breast cancer cell line MCF-7was incubatedwith50nmol/L gemcitabine for0,3,7,10,13and16days，the expression of CN-Ⅱ andAPE/Ref-1in human breast cancer cell line MCF-7were elevated significantly both atmRNA and protein levels，and were positively correlated with incubation time, whichis consistent with the propprtion of apototic cells. And the expression of CN-Ⅱ andAPE/Ref-1were increasing significantly from tenthdays, reaching the highest insixteenth days. And when the drug resistant cells was compared with the non-drugresistant cells, which were both incubated with50nmol/L gemcitabine for10,13and16days, the expression of mRNA and protein of CN-Ⅱ and APE/Ref-1in drugresistant cells have statistical significance.（P<0.05）Conclusion：The obvious up-regulated expression of CN-Ⅱ and APE/Ref-1maybe an adaptive response contributing to the overall chemoresistance in breast cancer，which implies that the targeted intervention on CN-Ⅱ and APE/Ref-1may help toincrease the chemosensitivity in breast cancer．... |
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