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Currently there are four organic intercalators approved by the FDA for the treatment of human cancers:

1:
Daunorubicin (sold under the brand names of Cerubidine® and Daunoxone® and the generic name Daunorubicin hydrochloride)

2:
Doxorubicin (sold under the brand name Adriamycin PFS®, Adriamycin RDF®, Rubex® and the generic name Doxorubicin hydrochloride)

3:
Mitoxantrone (sold under the brand name Novanthrone ® and its generic name)

4:
Amsacrine

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13073456851

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Subcellular daunorubicin distribution and its relation to multidrug resistance phenotype in drug¡ªresistant cell line SMMC¡ª7721£¯R
Õª¡¡Òª:AIM£ºTo investigate the correlation between subcellular daunorubicin distribution and the multidrug resistance phenotype in drug-resistant cell line SMMC-7721/R.METHODS:The multidrug resistant cell line SMMC-7721/R,a human hepatocellular carcinoma cell line,was established.Antisenes oligonucleotides(AS-ODN)were used to obtain different multidrug resistance phenotypes by inhibiting the expression of mdr1 gene and/or multidrug resistance-related protein gene(mrp)using Lipofectamine as delivery agent.Expression of mdr1 and mrp genes was evaluated by RT-PCRand Western blotting.Intracellular daunorubicn(DNR)concentration was measured by flow cytometry.Subcellular DNR distribution was analyzed by confocal laser scanning microscopy.Adriamycin(ADM)and DNR sensitivity was examined by MTTmethod.RESULTS:Low level expression of mdr1 and mrpmRNAs and no expression of P-Glycoprotein(P-gp)and multidrug resistance-related protein(P190)were detected in parental sensitive cells SMMC-7721/S,but over-expression of these two genes was observed in drug-resistant cell SMMC-7721/R,The expression of mdr1 and mrp genes in SMMC-7721/Rcells was down-regulated to the level in the SMMC-7721/Scells by AS-ODN.Intracellular DNAconcentration in SMMC-7721/Scells was 10times higher than that in SMMC-7721/Rcells.In SMMC7721/Scells intracellular DNA distributed evenly in the nucleus and cytoplasm.while in SMMC-7721/Rcells DNR distributed in a punctate pattern in the cytoplasm and was reduced in the nucleus.DNR concentration in SMMC-7721/Rcells co-transfected with AS-ODNs targeting to mdr1and rpmRNAs recovered to 25percent of that in SMMC7721/Scells.Intracellular DNA distribution pattern in drug-resistant cells treated by AS-ODN was similar to drug-sensitive cell.and the cells resistance index(RI)to DNA and AMD decreased at most from 88.0and 116.0to4.0and 2.3,repectively.Co-Transfection of two AS-ODNs showed a stronger synergistic effect than separate transfection.CONCLUSIONS-gp and P190are two members mediatingMDR in cellline SMMC7721/R,Intracellular drug concentration increase and subcellular distribution change are two important factos in multidrug resistance(MDR)formation.The second facto,drugs transport by P-gp andP190from cell nucleus to organell in cytoplasm,may play a more important role.
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2Â¥2007-07-18 17:03:13
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13073456851

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SOMATOSTATIN MAY ENHANCE CYTOTOXIC EFFECT OF DOXORUBICIN ON GALLBLADDER CANCER CELLSÀî¼ÃÓî[1] ȫ־ΰ[1] ÕÅÇ¿[2] Áõ½¨ÎÄ[2][1]DepartmentofGeneralSurgery,XinhuaHospital,ShanghaiSecondMedicalUniversity,Shanghai200092 [2]StateKeyLaboratoryofBioreactorEngineering,NewWorldInstituteofBiotechnology,EastChinaUniversityofScienceandTechnology,Shanghai200237Õª¡¡Òª:Objective: To explore the change of chemosensitivity of gallbladder cancer cells pre-treated with somatostatin. Methods: Twenty-four hours after somatostatin treatment, gradient concentrated Doxorubicin was added and growth curve of gallbladder cancer cells was investigated to measure IC50, i.e.,concentration of l)oxorubicin at 50% cell viability.Results: Somatostatin ccould induce gallbladder cancer cell growth arrest in S phase. Inhibition of growth of cancer cell line was detected by Doxorubicin concentration- dependently (P<0.05). IC50 value was significantly lower by combined-treating with somatostatin and Doxorubicin compared with by Doxorubicin alone (P<0.05). Conclusion: Somatostatin could increase the cytotoxic effect of Doxorubicin on gallbladder cancer cell by modulating its cell cycle.

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