PRDX6 knockdown sensitizes multiple myeloma cells to ferroptosis through inactivation of the PI3K/AKT pathway

Area of Science:

• Oncology
• Cell Death Mechanisms
• Molecular Biology

Background:

• Multiple myeloma (MM) is a hematologic malignancy.
• Ferroptosis is a regulated form of cell death.
• The role of Peroxiredoxin-6 (PRDX6) in MM ferroptosis is not fully understood.

Purpose of the Study:

• To investigate the impact of PRDX6 on ferroptosis in multiple myeloma.
• To elucidate the underlying mechanisms of PRDX6-mediated ferroptosis in MM.
• To assess the therapeutic potential of targeting PRDX6 in MM.

Main Methods:

• PRDX6 expression was analyzed in MM cells using Western blotting and qRT-PCR.
• MM cells were treated with PRDX6 shRNA, ferroptosis inducers/inhibitors (Erastin/ferrostatin-1), and a PI3K/AKT pathway activator (740Y-P).
• Cell viability, apoptosis, iron levels, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), SLC7A11, GPX4, and PI3K/AKT pathway molecules were assessed.

Main Results:

• PRDX6 expression was significantly elevated in MM cells.
• PRDX6 silencing sensitized MM cells to ferroptosis, evidenced by increased Fe2+, ROS, and MDA, and decreased GSH, SLC7A11, and GPX4.
• 740Y-P treatment reversed these ferroptosis-associated changes, and PRDX6 knockdown reduced PI3K/AKT pathway activity.

Conclusions:

• PRDX6 knockdown induces pro-ferroptotic effects in MM cells.
• This effect is mediated by the inactivation of the PI3K/AKT pathway.
• PRDX6 represents a promising therapeutic target for multiple myeloma treatment.