الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 125 |  |  |
| | | from | 125 | | |
Abstract
Apigenin has different effects on inflammation and tumor tissues. Its effect on colon cancer is still slightly known. So we aimed in this study to assess the effect of Apigenin-liposomes on the expression of programmed cell death ligand 1 (PD-L1), an immune checkpoint that facilitates tumor escape from the immune system. In addition, we intended to determine the expression of cancer stem cell marker (CD-133) under the effect of this novel immunotherapeutic agent.
For this purpose, twenty Egyptian cancer colon patients were recruited from the Department of Surgery, Main Alexandria University Hospital, Egypt. Tumor and paraneoplastic tissues, as well as blood samples were taken from each patient during and beforesurgical resection respectively. We designed a tissue culture system composed of fresh tumor samples and their paraneoplastic normal tissues to clearly reflect the primary condition of the tumor microenvirnoment.
Both fresh tissues of tumor and surrounding samples were cultured with and without Apigenin-liposomesfor 24hrs. Apigenin-liposomes were prepared using thin film hydration method for development of stable liposomal nano-carrier with high encapsulation of the hydrophobic flavone Apigenin for enhanced chemotherapeutic effects.
After the incubation period, tumor and surroundingtissues were then fixed in 10% neutral-buffered formalinfor 24 hours. Then samples were embedded in paraffin blocks. Then we measured the effect of Apigenin- liposomes on CD-133 and PD-L1 expression by semi-quantitative immunohistochemical detection of both biomarkers using rabbit monoclonal antibodies. Final detection was done using a labeled streptavidin-biotin immunoenzymatic antigen detection system.
Results of the present study showed that PD-L1 expression was inhibited in tissue cultures supplemented with Apigenin-liposomes, twelve samples showed negative expression, and eight samples were weakly or moderately positive. No strongly expressed samples were recored under the effect of Apigenin-liposomes. This indicates that Apigenin-liposomes had the ability to reduce and modify PD-L1 expression in colon cancer.
Our data showed also that the effect of Apigenin-liposomes on PD-L1 expression did not have a relation to tumor clinicopathological characteristics including histological grade, cancer stage, lymph node involvement and vascular metastasis. It was not also correlated to age, sex, duration of illness or studied laboratory data.
Moreover, CD-133 expression was noticed in all untreated tumor samples and number of untreated surrounding samples. However, Apigenin-liposomes altered this expression in vitro. All surrounding tissues showed negative expression of CD-133 under the effect of Apigenin-liposomes.Additionally, tumor tissues showed negative expression in 13 samples, with mild to moderate expression in 5 samples. Only two samples showed strong positive expression. This indicates a promicing impact of Apigenin-liposomes on the expression of the colorectal stem cell marker.