Bazedoxifene enhances paclitaxel efficacy to suppress glioblastoma via altering Hippo/YAP pathway

Area of Science:

• Neuro-oncology
• Cancer pharmacology
• Molecular biology

Background:

• Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with limited treatment options.
• Novel therapeutic strategies are urgently needed to improve patient outcomes.
• Targeting GBM cell survival and invasion pathways is a key research area.

Purpose of the Study:

• To investigate the efficacy of bazedoxifene as a monotherapy and in combination with paclitaxel for glioblastoma.
• To elucidate the underlying molecular mechanisms of bazedoxifene's action on glioblastoma cells.
• To evaluate the therapeutic potential of this combination in preclinical models.

Main Methods:

• In vitro studies assessing glioblastoma cell survival, invasion, apoptosis, and epithelial-mesenchymal transition (EMT).
• Analysis of YAP phosphorylation and inactivation.
• In vivo evaluation using a preclinical animal model of glioblastoma.

Main Results:

• Bazedoxifene significantly reduced glioblastoma cell survival and invasion.
• The combination of bazedoxifene and paclitaxel demonstrated superior efficacy in suppressing glioblastoma progression.
• Combined treatment promoted apoptosis, reduced EMT, and accelerated YAP phosphorylation and inactivation.
• Preclinical animal models validated the in vitro findings.

Conclusions:

• Bazedoxifene exhibits anti-glioblastoma activity by inhibiting cell survival and invasion.
• The combination of bazedoxifene and paclitaxel offers a synergistic approach to combat glioblastoma progression.
• This study provides a strong rationale for developing bazedoxifene-based therapies for GBM patients.