الفهرس 
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Abstract
Apigenin is one of the most bioactive plant flavones. Its consumption through diet is highly recommended, especially with several health disorders. AP has been demonstrated to help in stimulating immune system and provide some protection against cancer.
AP shows significant selective cell cytotoxicity against various types of cancer cells with low or no toxicity to normal cells. These selective anti-cancer effects are further shown to suppress cancer stem cells (CSCs) in various types of cancers. CSCs are closely associated with drug resistance, metastasis and the recurrence of cancer. In addition, its effect on the expression of programmed cell death- ligand 1 (PD-L1) an immune checkpoint that facilitates tumor escape from the immune system is recorded. So, in this study the biomarkers PD-L1 and CD-133 level of expression were evaluated under the effect of AP on BC cells and BCSCs, using immuno-histochemical techniques. AP was loaded on liposomes NPs to overcome its solubility, metabolic and bioavailability problems.
For this purpose, twenty Egyptian females who were scheduled for modified radical mastectomy for histologically proved breast cancer were recruited from department of Surgery, Medical Research Institute, Alexandria University. Smokers, diabetics and hypertensive patients were excluded. Patients were free from any viral, bacterial or parasitic infection; neither of them had an immunologic mediated disease that might have influenced the normal behavior of immunocompetent individuals.
Both fresh tissues of tumor and paraneoplastic samples were cultured with AP nanoparticles for 24hrs.AP nanoparticles were prepared using thin film hydration method for development of stable liposomal nanocarrier with high encapsulation of the hydrophobic flavone AP.
After the incubation period, tumor and paraneoplastic tissue were then fixed in 10% phosphate-buffered formalin for 24 hours. Then samples were embedded in paraffin blocks. Then we measured the effect of AP nanoparticles on CD-133 and PD-L1 expression by semi-quantitative immunohistochemical detection of both biomarkers.
Our results showed, significant reduction in both biomarkers (PD-L1 and CD-133) expression after incubation with AP-NPs.
Results showed an increased effect of AP-NP related to tumor grade, stage and vascular invasion as regards PD-L1 expression.
However, a non-significant difference in level of expression of CD-133 and any of the clinico-pathologicalparameters.
In conclusion, these results suggest a potential role of Apigenin nanoparticles in breast cancer immunotherapy, as a novel agent to suppress immune checkpoints, hindering tumor escape from the appropriate immune response and enhancing an effective immune reaction. Finally, our data exhibited a highlight to Apigenin’s key role in treatment of breast cancer and its remarkable functional activities.