الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 141 |  |  |
| | | from | 141 | | |
Abstract
Introduction:
Breast cancer (BC) is the most common cancer type and the second most frequent cause of cancer-related death in women. The most conventional strategies for cancer therapy involve surgery, radiotherapy and chemotherapy. Radiotherapy is highly toxic and damage adjacent healthy cells. Side effects may be acute (occurring within few weeks after therapy), intermediate or late (occurring months or years after the therapy). Hence, seeking for new therapeutic agents and effective therapies to prevent or control the complications and side effects of routine drugs is of a central importance.
Aim of the work:
The main target of this study was to investigate the antitumor potentiality of F. arabica ethanolic extract (FAEE) in comparison to single high dose of radiation (6Gy) and their effects on protein levels of phosphorylated AKT, phosphorylated FOXO3a and gene expression of Bcl-2 on mice bearing Ehrlich Ascites Carcinoma (EAC).
Material and Methods
This study was an in vivo study employing 120 balb-c mice that divided into 6 groups:
group (I): Included 10 normal control mice.
group (II): Included 30 normal mice each 10 mice were received different dose of Fagonia arabica ethanolic extract (FAEE) (250,500,1000mg/kg/day) once daily via oral intubation for a period of 14 days.
group (III): Included 10 Ehrlich carcinoma bearing mice.
group (IV): Included 10 EC-bearing mice exposed to a single dose (6Gy at a dose rate 300 Mu/min) of ionizing radiation at tumor localization.
group (V): Included 30 EC-bearing mice, each 10 mice were received different dose of FAEE (250,500,1000mg/kg/day) once daily via oral intubation for a period of 14 days.
group (VI): Included 30 EC-bearing mice, each 10 mice were received different dose of FAEE (250,500,1000mg/kg/day and exposed after 2 hours to a single dose (6Gy at a dose rate 300 Mu/min) of ionizing radiation at tumor localization,FAEE administration was then continued once daily via oral intubation for 14 consecutive days.
At the end of the study body weight, tumor volume and tumor growth rate were estimated and followed by:
• The activities of liver enzymes AST, ALT, TAC and MDA were measured in serum usingcommercially available local diagnostic kits.
• Tissue homogenate phosphorylated FOXO3a and AKT protein level were assessed by using ELISA technique.
• Bcl-2 gene expression was assessed by real-time reverse transcription polymerase chain reaction (RT-PCR).
• Histopathological study: tumor tissue was excised, fixed in 10 % neutral formalin, embedded in paraffin blocks and sectioned. Tissue sections were stained with Hematoxylin and Eosin (H&E) stain and examined using light microscope.
Results and Discussion:
In this study our results revealed that EC-bearing mice supplemented with FAEE and/or radiation result in decrease in tumor volume, tumor growth rate and body weight gain in a dose dependent manner. These results are in agreement with previous studies indicated that Zygophyllaceous family exhibit anti-proliferative effect against human breast cancer MCF-7 cell line and this effect was mediated through interference with normal cell cycle distribution and induction of apoptosis. This suggests that FAEE may be an effective antitumor agent against breast cancer.
Combination of different doses of FAEE with ionizing radiation significantly increase radiation induce tumor damage reflected by decrease tumor volume and tumor growth rate in comparison to radiation only treated EC-mice. This suggests that FAEE exerts radiosensitizer effect especially at dose of 500 mg/kg.
Additionally, the results of the present study demonstrated that, significant elevation of p-AKT and p- FOXO3a in untreated EC-bearing mice was observed. Moreover, we noticed significant decrease in the concentration of p-AKT and p- FOXO3a in EC-mice treated with radiation or after FAEE administration in a dose dependent manner, while FAEE administration at 1000 mg/Kg significantly decrease p-AKT and p- FOXO3a than radiation only treated mice. This was reflecting the inhibitory effect of FAEE on p-AKT and p- FOXO3a.
In this study we evaluated the effect of FAEE and/or Radiation on Bcl-2 gene expression in EC-bearing mice. The results revealed that FAEE alone or in combination with radiation significantly lower gene expression of Bcl-2 than that in untreated EC- bearing mice.
Moreover, the results of the present study revealed that supplementation withFAEE significantly decreases MDA levels and increase TAC levels in comparison to untreated EC- bearing mice. This result demonstrating the potential of FAEE administration in attenuation of oxidative stress via free radical scavenger activity in EC-bearing mice. Furthermore, In the present study elevated levels of ALT, and AST in untreated EC-bearing mice were observed. Such increase may be interpreted as a result of hepatocellular damage by Ehrlich carcinoma.FAEE administration at all doses restored the elevated biochemical parameters to normal range, indicating the protected effect of FAEE against tumor cell induced hepatotoxicity.