Bortezomib-enhanced radiosensitization through the suppression of radiation-induced nuclear factor-κB activity in...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Oral cancer exhibits elevated nuclear factor-κB (NF-κB) activity, a key driver of tumor growth.
• NF-κB inhibition is a validated strategy for suppressing oral cancer progression.
• Bortezomib, a proteasome inhibitor, targets NF-κB and is used in molecular-targeted therapy.

Purpose of the Study:

• To investigate bortezomib's efficacy as a proliferation inhibitor and radiosensitizer in oral cancer treatment.
• To evaluate the combined effects of bortezomib and radiation (RT) on oral cancer growth.
• To elucidate the molecular mechanisms underlying bortezomib's anti-tumor effects.

Main Methods:

• Assessed NF-κB activity and cell proliferation inhibition by bortezomib in vitro and in vivo.
• Evaluated the combined effects of bortezomib and RT on oral cancer cell growth.
• Utilized ELISA to examine downstream signaling molecules, including angiogenic factors and anti-apoptotic proteins.
• Measured cleaved poly(ADP-ribose) polymerase expression to assess apoptosis induction.

Main Results:

• Bortezomib significantly inhibited NF-κB activity and oral cancer cell proliferation.
• Combined bortezomib and RT treatment demonstrated superior suppression of NF-κB activity and tumor growth compared to RT alone.
• The combination therapy markedly reduced radiation-induced pro-angiogenic factors and tumor vascularization.
• Bortezomib counteracted RT-induced upregulation of anti-apoptotic proteins and enhanced apoptosis induction.

Conclusions:

• Bortezomib is a potent inhibitor of oral cancer growth, both alone and in combination with radiation.
• The combined treatment strategy effectively suppresses tumor proliferation, angiogenesis, and promotes apoptosis.
• Targeting NF-κB with bortezomib represents a promising novel molecular therapy for oral cancer.