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

• Main Authors: Jie LV, Yufeng TIAN
• Format: Article
• Language: zho
• Published: Chinese Anti-Cancer Association; Chinese Antituberculosis Association 2012-09-01
• Series: Chinese Journal of Lung Cancer
• Subjects: Src tyrosine kinase; A549/DDP; Multi-drug resistance; MDR1; LRP
• Online Access: http://dx.doi.org/10.3779/j.issn.1009-3419.2012.09.01
• ISSN: 1009-3419; 1999-6187

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.