The multidrug resistance can be reversed for the decrease of P-gp and LRP by inhibiting PI3K/Akt/NF-κB signal pathway...

Area of Science:

• Oncology
• Molecular Biology
• Cellular Signaling

Background:

• Nasopharyngeal carcinoma (NPC) often develops multidrug resistance (MDR).
• The PI3K/Akt/NF-κB signaling pathway is implicated in various cellular processes, including drug resistance.
• P-glycoprotein (P-gp) and Lung Resistance-Related Protein (LRP) are key efflux pumps associated with MDR.

Purpose of the Study:

• To elucidate the role of the PI3K/Akt/NF-κB signaling pathway in the expression of P-gp and LRP in NPC MDR cells.
• To investigate whether modulating this pathway affects NPC drug resistance.

Main Methods:

• Western blot was used to detect the activity of the PI3K/Akt/NF-κB pathway (PI3K, p-Akt, NF-κB/p65).
• Real-time PCR and Western blot were employed to measure the expression levels of P-gp and LRP.
• Specific inhibitors (LY-294002 for PI3K and PDTC for NF-κB) were used to modulate pathway activity.

Main Results:

• NPC cells (CNE/DDP) exhibited increased expression of PI3K, p-Akt, NF-κB/p65, P-gp, and LRP, along with elevated mRNA levels of P-gp and LRP.
• Inhibition of the PI3K/Akt/NF-κB pathway using LY-294002 and PDTC led to decreased expression of p-Akt, NF-κB p65, and consequently, reduced mRNA levels of P-gp and LRP.
• Drug resistance indices (RIs) were significantly reduced in inhibitor-treated groups compared to the CNE/DDP group.

Conclusions:

• Activation of the PI3K/Akt/NF-κB pathway upregulates P-gp and LRP expression, contributing to multidrug resistance in nasopharyngeal carcinoma.
• Inhibition of the PI3K/Akt/NF-κB signaling pathway can reverse multidrug resistance in nasopharyngeal carcinoma cells, suggesting its potential as a therapeutic target.