Proteasome inhibitors decrease paclitaxel‑induced cell death in nasopharyngeal carcinoma with the accumulation of...

Area of Science:

• Oncology
• Cancer Biology
• Pharmacology

Background:

• Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia.
• Paclitaxel is a primary treatment for advanced NPC.
• The interaction between proteasome inhibitors and paclitaxel in NPC requires investigation.

Purpose of the Study:

• To investigate the impact of proteasome inhibitors on paclitaxel's efficacy in NPC.
• To elucidate the underlying mechanisms of this interaction.

Main Methods:

• Cell Counting Kit-8 and flow cytometry assays were used.
• Western blotting was employed to analyze protein expression.
• The effects of proteasome inhibitors (PS341, MG132) and paclitaxel were assessed.

Main Results:

• Proteasome inhibitors (PS341, MG132) diminished paclitaxel's cytotoxic effects on NPC cells.
• These inhibitors reversed paclitaxel-induced cell cycle arrest and apoptosis.
• Accumulation of CDK1/cyclin B1 was observed, alongside decreased apoptosis signaling (MCL1, Caspase-9, PARP).

Conclusions:

• Proteasome inhibitors antagonize paclitaxel's therapeutic effect in NPC.
• CDK1/cyclin B1 dysfunction mediates the loss of paclitaxel's lethality.
• Combining paclitaxel with proteasome or CDK1 inhibitors may hinder effective NPC treatment.