Investigating the Promising Anticancer Activity of Cetuximab and Fenbendazole Combination as Dual CBS and VEGFR-2...

Area of Science:

• Pharmacology and Toxicology
• Molecular Biology
• Cancer Research

Background:

• Monoclonal antibodies like Cetuximab (Ce) are vital in cancer therapy.
• Fenbendazole (Fen), an antiparasitic drug, shows emerging anti-cancer properties.
• Investigating combination therapies can reveal synergistic effects and novel treatment strategies.

Purpose of the Study:

• To evaluate the cytotoxic effects of Cetuximab (Ce) and Fenbendazole (Fen) individually and in combination.
• To explore the molecular mechanisms underlying the anti-cancer activity of Ce and Fen, including target interactions and gene expression.
• To assess the potential of this combination therapy for cancer treatment.

Main Methods:

• Cytotoxicity assessed via MTT assay.
• Colchicine-tubulin binding, VEGFR-2 inhibition, qRT-PCR for apoptosis-related genes (p53, Bax, Bcl-2), ROS level determination, cell cycle analysis, and Annexin V apoptosis assay were performed.
• Molecular docking studies were conducted for Fen interactions with colchicine binding site (CBS) and VEGFR-2.

Main Results:

• The combination of Cetuximab and Fenbendazole exhibited significant synergistic cytotoxicity compared to individual treatments.
• The combination therapy demonstrated enhanced apoptosis induction, cell cycle arrest, and modulation of ROS levels.
• Molecular docking confirmed potential interactions of Fen with tubulin and VEGFR-2, supporting observed anti-cancer effects.

Conclusions:

• Cetuximab and Fenbendazole combination therapy shows potent anti-cancer activity.
• The synergistic effect is mediated through multiple pathways, including tubulin binding, VEGFR-2 inhibition, and apoptosis induction.
• This combination represents a promising strategy for further investigation in cancer treatment.