Inhibition of the JNK pathway downregulates lung-resistance pro-tein and enhances the chemosensitivity of A549 cells to cisplatin / 中国肿瘤临床

ABSTRACT

Objective: To investigate the relationship between the c-Jun N-terminal kinase (JNK) pathway and lung-resistance protein (LRP). Methods:A549 cells were treated with various concentrations of CDDP for 72 h. The LRP mRNA expression was then analyzed using reverse transcription PCR (RT-PCR). LRP, JNK, and P-JNK were analyzed by Western blotting. The A549 cells were then pretreated with SP600125 (2 μg/ml to 4 μg/ml ) for 1 h. Afterward, CDDP (16 μg/ml) was added into the culture for 72 h. A Cell Counting Kit-8 was used to investigate the sensitivity of CDDP to the A549 cells. Flow cytometry was used to detect the apoptosis rate. The LRP mRNA expression was analyzed using RT-PCR. LRP, JNK, and P-JNK were analyzed by Western blotting. Results:CDDP in-duced the mRNA and protein expression of both LRP and P-JNK in a dose-dependent manner. Pretreatment with SP600125 enhanced the sensitivity of CDDP to the A549 cells and increased the apoptosis rate. However, the LRP mRNA and LRP expression in the pre-treated cells was lower than that in the presence of CDDP alone. Conclusion:In A549 cells, CDDP induces the LRP expression via the JNK pathway. This result suggests that lung cancer therapy can be improved by the addition of CDDP to inhibit the JNK signaling path-way.