Blocking the Glycolytic Pathway Sensitizes Breast Cancer to Sonodynamic Therapy

Area of Science:

• Oncology
• Biochemistry
• Nanomedicine

Background:

• Targeting cancer cell aerobic glycolysis is a key therapeutic strategy but faces limitations due to systemic toxicity.
• Dual inhibition of glycolysis and mitochondrial function offers a potential approach to overcome these limitations.
• Sonodynamic therapy (SDT) is an emerging cancer treatment that induces mitochondria-dependent cell damage.

Purpose of the Study:

• To investigate the combined efficacy of SDT and 2-deoxyglucose (2DG) against breast cancer.
• To evaluate the effects of this combination therapy on cancer cell viability, apoptosis, and energy metabolism.
• To assess the in vivo therapeutic effects and toxicological profile of SDT + 2DG treatment.

Main Methods:

• In vitro studies on breast cancer cells assessing cell viability, apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), and ATP production.
• In vivo studies involving tumor-bearing models to evaluate tumor volume and weight reduction.
• Toxicology tests to assess the safety of sinoporphyrin sodium and 2DG dosages.

Main Results:

• SDT + 2DG co-treatment significantly reduced breast cancer cell viability and increased apoptosis compared to single treatments.
• The combination therapy enhanced ROS generation, reduced MMP, inhibited oxidative phosphorylation, and blocked ATP provision.
• In vivo, SDT + 2DG markedly reduced tumor volume and weight, with tolerable toxicity profiles for both agents.

Conclusions:

• The combination of SDT and 2DG demonstrates significant anti-cancer effects against breast cancer by targeting both glycolysis and mitochondrial function.
• This dual-targeting strategy offers a promising therapeutic approach for highly metastatic breast cancer.
• The tolerable toxicity suggests potential clinical applicability for SDT + 2DG therapy.