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• W2347489968 abstract "Objective： This study was designed to investigate the effectiveness of natural and naphthyl imide- conjugated antisense oligonucleotide on inhibiting mdr1 gene expression and of overcome the problem of multidrug resistance in human epidemic carcinomata anti- adriamycin cells(KB－ A－ 1). Methods： A novel naphthyl imide- conjugated mdr1 antisense oligonucleotide was synthesized by S- alkylation reaction. Compared with the natural one, the effectiveness of naphthyl imide- conjugated mdr1 antisense oligonucleotide on inhibiting the multidrug resistance was detected by MTT colometric assay and ELISA. Results： The abilities of antisense oligonucleotides to inhibit the cell growth of KB- A- 1 mainly depended upon their targeted sequences selected. The inhibiting rates to KB- A- 1 cells of antisense oligonucleotides (from OligoⅠ to OligoⅣ ) which bind the targeted sequences of the translation initiation site of mdr1 were 13.34％ ,14.32％ ,26 00％， and 25.37％， respectively. Among four oligonucleotides, the activity of OligoⅢ to inhibit the growth of KB- A- 1 cell was the highest (P 0.01). Compared with the unmodified one,the inhibition of antisense oligonucleotides to the growth of KB- A- 1 cell was increased by conjugating with naphthyl imide. The ability of naphthyl imide- conjugated antisense oligonucleotide to resist serum- mediated nuclease was also increased as demonstrated by gel shift electrophoresis. The antisense oligonucleotide or its naphthyl imide conjugate could only inhibit the growth of KB- A- 1 cells and had no effect on the growth of KB- 3- 1 cells. So it could be inferred that the inhibition of KB- A- 1 cells was due to the repression of gene expression of mdr1 in KB- A- 1 cells by antisense oligonucleotide or its naphthyl imide conjugate. ELISA showed that the P- glycoprotein expressions were more strongly inhibited by naphthyl imide- conjugated oligonucleotide than that by unmodified oligonucleotide. Conclusion： Inhibition of human tumor cell growth was due to the inhibition of mdr1 gene expression and the reversal of multidrug resistance by antisense oligonucleotide and its naphthyl imide conjugated. 1,8- Naphthyl imide could improve the properties of natural oligonucleotide in inhibiting the multdrug resistance and resisting nuclease by covalently linkage at the end of oligonucleotide." @default.
• W2347489968 created "2016-06-24" @default.
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• W2347489968 date "2001-01-01" @default.
• W2347489968 modified "2023-09-23" @default.
• W2347489968 title "Inhibition of Multidrug Resistance in Human Tumor Cell by Naphthyl Imide- Conjugated Antisense Oligonucleotide" @default.
• W2347489968 hasPublicationYear "2001" @default.
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