Reversion of multidrug resistance in lung adenocarcinoma-resistant cell line A549／R by anti-sense strategy
- VernacularTitle:人肺腺癌细胞多药耐药逆转的反义策略
- Author:
Liangan CHEN
1
;
Youning LIU
Author Information
1. General Hospital of PLA
- From:
Chinese Journal of Lung Cancer
2001;4(3):165-168
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the possibility of reversion of multidrug resistance in lung adenocarcinoma-resistant cell line A549／R by antisense strategy including mdr1 antisense oligodeoxynucleotide and Ribozyme. Methods The target points, -9 to ＋6 in mdr1 cDNA sequence and GUC at 880 site of mdr1 mRNA were selected. Phosphorothioate antisense oligodeoxynucleotide and DNA of plasmid expressing anti-mdr1 Ribozyme（pHβApr-1 neo／mdr1-Rb ）corresponding to above target points were transfered into A549／R cell by lipofectin. The expression of mdr1 mRNA and Pgp, cellular rhodamine accumulation and sensitivity to doxorubicin were detected respectively in transfered cells and control cells by RT-PCR, flow cytometry, rhodamine test and MTT. Results Treatment of A549／R cell with antisense oligodeoxynucleotide and Ribozyme led to decrease of mdr1 mRNA and Pgp expression, increase of rhodamine cellular accumulation, and 20-180 fold increase of sensitivity to doxorubicin compared to control cell. Conclusion The mdr1 antisense oligodeoxynucleotide and Ribozyme are possessed with powerful effect on reversion of MDR in lung adenocarcinoma-resistant cell A549／R by inhibiting mdr1 transcription, cleaving mdr1 mRNA and decreasing Pgp expression. Antisense strategy is a promising method of reversion of multidrug resistance in lung cancer.
