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Effect of Src Tyrosine Kinase Inhibition on the Drug-resistance as well as MDR1 and LRP Expression of the Human Cis-platinum-resistant Lung Cancer Cell Line A549/DDP
- Source :
- Chinese Journal of Lung Cancer, Vol 15, Iss 9, Pp 501-506 (2012)
- Publication Year :
- 2012
- Publisher :
- Chinese Anti-Cancer Association; Chinese Antituberculosis Association, 2012.
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Abstract
- Background and objective The aim of this study is to investigate the effect of Src tyrosine kinase inhibition on the drug-resistance as well as the expression of multidrug resistance 1 (MDR1) and lung resistance-related protein (LRP) of the human cis-platinum-resistant lung cancer cell line A549/DDP. Methods 4-Anilinoquirazoline was used to inhibit Src tyrosine kinase activity in A549/DDP. Western blot analysis was used to detect the Src tyrosine kinase activity. CellTiter-Glo assay was used to detect the drug sensitivity of tumor cells. Flow cytometry was used to detect the intracellular Rh-123 content. Western blot and real-time PCR assay were used to detect the expression of tumor MDR1 and LRP. Results 4-Anilinoquirazoline can down-regulate the cellular Src tyrosine kinase activity in A549/DDP. After treatment with 2.5 μM and 10 μM of 4-anilinoquirazoline, the cells became more sensitive to the drug and the reversal folds (RFs) of tumor cell sensitivity to the drug were 1.59- and 2.10-fold, respectively. The intracellular content of Rh-123 improved by 1.21- and 1.59-fold, respectively. The mRNA levels of MDR1 were 53.8% and 27.5% of the control, respectively. The mRNA level of LRP was 59.3% and 21.4% of the control, respectively. The expression of MDR1 and LRP protein significantly decreased. Conclusion The inhibition of Src tyrosine kinase activity in A549/DDP cells can reverse multi-drug resistance and increase the sensitivity of the cells to the drug. The mechanism may be related to the down-regulation of cellular MDR1 and LRP.
Details
- Language :
- Chinese
- ISSN :
- 10093419 and 19996187
- Volume :
- 15
- Issue :
- 9
- Database :
- Directory of Open Access Journals
- Journal :
- Chinese Journal of Lung Cancer
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.47b1da764654481963bd7ab12d518b7
- Document Type :
- article
- Full Text :
- https://doi.org/10.3779/j.issn.1009-3419.2012.09.01