Relationship Between Nf-κb Expression And Cisplatin Resistance In Lung Adenocarcinoma Cells And Mechanism Of Evodiamine In Reversion Of Multidrug Resistance

【Objective】This study was to evaluate whether Evodiamine could reverse the multidrug resistance(MDR) through inhibition of NF-κB signaling pathway in human lung adenocarcinoma cell line A549/DDP.【Methods】There were six groups in the examination of cellular level (A549 +DDP group , A549 +EV group , A549 +EV +DDP group A549/DDP +DDP group, A549/DDP +EV group and A549/DDP +EV +DDP group). Cytostasis was analyzed using MTT assay, and then calculates the IC50 and the drug resistance reversal fold. Apoptosis was analyzed using flow cytometry. Measure the expression of NF-κB by immunohistochemical technique and real-time PCR after incubation of A549/DDP cells with Evodiamine (0.125mg/L) or DDP (2ug/ml) at different time points. The mRNA expression of MDR1, NF-κB, BCL-2, MMP2,VEGF was measured by reverse transcriptase polymerase chain reaction (RT-PCR). Expressions of pIκB-α,pIKKαwere detected using Western blot.【Results】The resistance of A549/DDP cells to DDP was 8.075 folds. When added 0.125mg/L, 0.25mg/L EV, the drug resistance reversal of A549/DDP cells to DDP was increased to 3.668, 11.48 folds. Evodiamine can increase the chemo- sensitivity of A549/DDP cells to DDP. The expression of mRNA NF-κB was in an EV concentration-dependent and time-dependant manner. In A549/DDP cells, evodiamine inhibited IκBαphosphorylation also in a concentration-dependent and time-dependant manner, but pIKKαwas not in the same situation.【Conclusion】Evodiamine can influence NF-κB signaling pathway, leading to suppression of proliferation.induction of apoptosis and an increase of the sensitivity of lung adenocarcinoma cell lines A549/DDP towards DDP.