Targeting Microtubule-Associated Protein Tau in Chemotherapy-Resistant Models of High-Grade Serous Ovarian Carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• High-grade serous ovarian carcinoma (HGSOC) is a deadly gynecologic malignancy.
• Chemotherapy resistance, particularly to platinum and paclitaxel, is a major challenge in advanced HGSOC.
• Microtubule-associated protein tau (tau) expression is implicated in paclitaxel resistance.

Purpose of the Study:

• To investigate the role of tau in platinum/paclitaxel-resistant HGSOC.
• To evaluate the therapeutic potential of reducing tau expression using leucomethylene blue (LMB).
• To assess the synergistic effect of LMB and paclitaxel in HGSOC models.

Main Methods:

• Development of platinum/paclitaxel-resistant HGSOC cell culture and xenograft models.
• Quantification of tau and its phosphorylated species (phosphoSer396, phosphoThr181).
• Treatment with leucomethylene blue alone and in combination with paclitaxel.
• Assessment of cytotoxicity, tumor burden, and cancer cell elimination.

Main Results:

• Tau was overexpressed in platinum/paclitaxel-resistant HGSOC models.
• Leucomethylene blue reduced tau levels, exhibited cytotoxicity, and decreased tumor burden in vivo.
• The combination of leucomethylene blue and paclitaxel demonstrated synergistic anti-cancer effects.

Conclusions:

• Tau overexpression is a feature of resistant HGSOC.
• Targeting tau with leucomethylene blue is a feasible therapeutic strategy.
• Combination therapy with leucomethylene blue and paclitaxel offers a promising approach for terminal-stage HGSOC.