🔬 Introduction
Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Among its subtypes, Triple-Negative Breast Cancer (TNBC) is particularly aggressive due to the absence of estrogen, progesterone, and HER2 receptors, making targeted therapy challenging.
Apoptosis resistance and enhanced angiogenesis are two major hallmarks of TNBC progression. Targeting both pathways simultaneously may offer a more effective therapeutic strategy.
This study, published in BMC Cancer (2026), investigates the combined therapeutic effects of Mefloquine (MEF) and Cisplatin (CIS), particularly using a novel niosomal drug delivery system.
🧪 Materials & Methods
🧫 In Vitro Analysis
Cell lines used:
MCF-7 (hormone-positive breast cancer)
MDA-MB-231 (TNBC)
Cytotoxicity evaluated via MTT assay
Apoptosis-related genes analyzed:
BAX
BCL-2
CASP3
CASP7
Angiogenesis markers measured:
VEGF
KDR (VEGFR-2)
ROS production assessed using flow cytometry
💻 In Silico Docking Studies
Molecular docking was performed using Molegro Virtual Docker (MVD) to analyze binding affinity of:
Cisplatin (CIS)
Mefloquine (MEF)
Free combination (CIS-MEF)
Niosomal formulation (CIS-NMEF)
Target proteins:
BAX (pro-apoptotic)
Bcl-2 (anti-apoptotic)
VEGFR (angiogenesis receptor)
🧴 Niosomal Formulation
Mefloquine was encapsulated in niosomes using microfluidic technology:
Average particle size: ~218 nm
Encapsulation efficiency: 87.21%
Stable for 6 months at 4°C
This nano-delivery system improves drug stability, cellular uptake, and sustained release.
📊 Key Findings
🔥 Enhanced Cytotoxicity
Combination therapy significantly reduced IC50 values.
Strong synergistic effect (CI < 1), especially in TNBC cells.
CIS-NMEF showed the strongest cytotoxic activity.
💀 Induction of Apoptosis
Compared to control:
✔ Significant upregulation of BAX and CASP3
✔ Significant downregulation of BCL-2
✔ Activation of mitochondrial apoptotic pathway
CIS-NMEF demonstrated the strongest pro-apoptotic effect.
🌱 Inhibition of Angiogenesis
Treatment resulted in:
⬇ Decreased VEGF expression
⬇ Reduced KDR (VEGFR-2) levels
This suggests effective suppression of tumor vascularization.
⚡ Increased ROS Production
Significant ROS elevation in treated cells
Highest ROS observed in CIS-NMEF group
Indicates oxidative stress-mediated cancer cell death
🧠 Molecular Docking Results
Docking scores demonstrated:
Stronger binding affinity of MEF compared to CIS alone
Even stronger affinity in combination therapy
Niosomal combination showed the most stable interaction with:
BAX
Bcl-2
VEGFR
These findings confirm mechanistic synergy at the molecular level.
🎯 Conclusion
The niosomal formulation of Mefloquine significantly enhances the anticancer efficacy of Cisplatin by:
Promoting apoptosis
Suppressing angiogenesis
Increasing oxidative stress
Overcoming potential cisplatin resistance
CIS-NMEF emerges as a promising chemosensitizing strategy, particularly for aggressive TNBC.
Further in vivo and clinical studies are warranted to validate its translational potential.
📄 Full Article Reference
Title: Niosomal Mefloquine and Cisplatin in Breast Cancer: Comparative Effects on Apoptosis and Angiogenesis via In Vitro and In Silico Analysis
Journal: BMC Cancer, 2025
DOI: https://doi.org/10.1186/s12885-025-15372-6
