The role of eicosapentaenoic acid-loaded nanoparticles on alleviating drug resistance in xenograft breast cancer model.

BACKGROUND

Multidrug resistance (MDR) is a major dilemma in the effective chemotherapy treatment of breast cancer. Potential strategies to combat MDR include inhibiting efflux pumps such as ATP-binding cassette (ABC) transporters and calcium channel pumps like transient receptor potential (TRP) channels and blocking the metastatic pathway by inhibiting the antiapoptotic proteins like Bcl-2, while enhancing the apoptotic proteins like caspase-3.

RESULTS

The results demonstrated that treatment with either EPA or EPA/PCL led to a marked suppression of doxorubicin resistance, as evidenced by a significant reduction in tumor size, measured by caliper, in the treated groups over the course of the experiment. Furthermore, the combination of EPA or EPA-loaded PCL with DOX modulated the expression of drug resistance genes and apoptotic pathways by targeting transient receptor potential canonical 5 (TRPC5), P-glycoprotein (P-gp), and Bcl-2, while simultaneously enhancing the expression of caspase-3. Additionally, nano-characterization of the PCL particles using transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis demonstrated their favorable stability and physicochemical properties.

CONCLUSION

The present study investigated the effect of eicosapentaenoic acid (EPA)-loaded polycaprolactone (PCL) in overcoming drug resistance when used in combination with doxorubicin (DOX), as compared to DOX alone and EPA in its original form. Interestingly, it reveals a promising approach to ameliorate the resistance of Doxorubicin in breast cancer.