| Researh backgroundMultidrug resistance(MDR) means cancer cells exposure to a single anticancer drug lead to cross-resistance to many other structurally and functionally unrelated anticancer drugs. As a result, greatly reduced the chemotherapy effect of anticancer drugs. Nowadays, MDR is a major obstacle in cancer therapy, especially treatment in heamatological malignancies mainly by means of chemotherapy. Reversal of MDR is a clinical important problem urgently to be resolved. Many mechanisms are now known contribute to MDR, include changes in drug transport eg. Permeability-glycoprotein (Pgp, P-170), Multidrug Resistance Associated Protein(MRP), Lung Resistance-related Protein(LRP), in metabolic detoxification eg. Glutathion(GSH) , in drug target eg. topoisomerase II(TopoII), in DNA repair, in apoptosis eg. bcl-2> P53 etc. Among these, the mechanism of Pgp/mdrl mediated was recognised earliestly and was researched most extensively. GSH and its enzyme systems not only play important roles in cellular drug detoxification and in the course of resisting oxidation, but also enhance the metabolism and transportation potency of anticancer drugs in cancer cells, the cancer cells then become drug resistance cells.Many methods of MDR reversal have been researched now. Even if Verapamil(VRP), Cyclosporine A(CSA) and its derivative PSC-833 play some roles in MDR reverasl, they have side effects such as heart toxicity, immunosuppression, kidney toxicity and alter the pharmacokinetics of anticancer drugs simultaneously. No perfect method of MDR reversal can be used in clinic as yet . Searching reversing agents which are more potent and low side effect and can overcome MDR are very important. When cancer cells develop resistance to one lipophilic anticancer drug,VIthey also become cross-resistance to other structurally unrelated lippophilic drugs. Using non-cytotoxic lipophilic drugs compete drug binding sites on Pgp with anticancer drugs of MDR then reverse MDR. Reports from other countries show that erythromycin(EM) can reverse MDR in vitro. Reports from our country show that there are some effects in solid tumor therapy with erythromycin. But report about MDR reversal mechanism by erythromycin is seldom. The traditional Chinese medicine become a new research direction in MDR reversal. Searching traditional Chinese medicines which are high effect and low toxicity to reverse MDR are very important. Our department got compound Chinese traditional medicine JieXinKang after many years researching. Results showed that JieXinKang had roles of drug resistance reversal, increased the chemotherapy effect, no side effect and toxicity in introduction to clinical use. How about its reversal mechanism? Is it related to Pgp/mdrl? Or related to enzymes or other mechanisms mediated MDR? We still unknown now , these worth to further research.K562/A02 cell line is a human leukemia cell line which has typical phenotype of MDR with biological property of Pgp high expression, mdrl mRNA high expression, TopoII low expression, GST activity high. The purposes of this work was to study on reversal mechanism of MDR in K562/A02 cell line by neferine(One of the main utility components of JieXinKang) and erythromycin with methods of high performance liquid chromatography(HPLC), biochemical analyses, immunohistochemical technique and reverse transcriptase-polymerase chain reaction (RT-PCR), to provide theoretically and experimental bases for clinical use.I. Influence on proliferation and cellular ADM concentration in K562/A02 cell line by neferine and erythromycinObjective To study the influence on proliferation and cellularVIIAdriamycin concentration in K562/A02 cell line by neferine and erythromycin. Methods Cytotoxicity was determined by MTT[3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyl tetrazolium bromide] assay. After incubated K562, K562/A02 cell line and K562/A02 cell line which were treated with Nef, EM, Nef+EM, Verapamil (VRP) in ADM for 1 or 3 hours, cellular ADM concentration was examined by...
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