Combination of Fish Oil and Selenium Enhances Anticancer Efficacy and Targets Multiple Signaling Pathways in...

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Fish oil (FO) and selenium (Se) exhibit antiangiogenic properties relevant to cancer therapy.
• Triple-negative breast cancer (TNBC) remains a challenging malignancy with limited targeted treatment options.
• Avastin (bevacizumab) is an antiangiogenic agent used in cancer treatment.

Purpose of the Study:

• To investigate the combined efficacy of fish oil (FO) and selenium (Se) with low-dose Avastin (bevacizumab) in a triple-negative breast cancer (TNBC) mouse model.
• To determine if the combination treatment enhances therapeutic effects in a dose-dependent manner.
• To elucidate the multiple signaling pathways targeted by the combination therapy.

Main Methods:

• Mice bearing TNBC were randomized into five groups: control, Avastin alone, and Avastin with low, medium, or high doses of FO/Se.
• Tumor growth and metastasis were assessed.
• Protein and mRNA expression of key signaling molecules, including those involved in angiogenesis, cytoplasmic signaling, and downstream targets, were measured.

Main Results:

• Combination treatment with FO/Se and Avastin significantly reduced tumor growth and metastasis compared to Avastin alone.
• Dose-dependent inhibition of proangiogenic factors, cytoplasmic signaling pathways (e.g., PI3K/AKT, Ras/ERK, STAT3), and downstream targets was observed.
• Key targets affected include EMT factors, cell cycle regulators, cancer stem cell markers, HSP-90, HIFs, MMP-9, and apoptosis induction.

Conclusions:

• Combination therapy of fish oil and selenium with Avastin demonstrates enhanced therapeutic efficacy against TNBC in a dose-dependent manner.
• The treatment effectively targets multiple signaling pathways involved in tumor growth, angiogenesis, metastasis, and cell survival.
• This combination strategy offers a promising approach for improving TNBC treatment outcomes.