الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Prostate cancer is the most frequent malignant tumor in the male population worldwide, as well as one of the most common among all the leading causes of cancer-related death. Although several men receive an early-stage disease diagnosis and run an indolent course, many cases are characterized by locally advanced or metastatic disease at the time of diagnosis.
Treatments for prostate cancer include surgery, radiation, and androgen deprivation, among other therapies. Often these therapies are used in combination with each other. Radiotherapy kills cancer cells by generating free radicals and reactive oxygen species (ROS) that progress to cause fatal cellular and DNA damage. Sometimes, more aggressive tumors often tend to be radioresistant.
In comparison with other models of prostate tumor cell lines, PC-3 cells have high metastatic potential. Although great success has been achieved on radiotherapy, there is still an intractable challenge to enhance radiation damage to tumor tissue and reduce side effects to healthy tissue. Radiosensitizers are chemicals or pharmaceutical agents that can enhance the killing effect on tumor cells by accelerating DNA damage and producing free radicals indirectly. In most cases, radiosensitizers have less effect on normal tissues.
Resveratrol, a polyphenol found in berries, nuts, and red wine, has a variety of cancer chemopreventive activities including anti- inflammatory, pro-apoptotic, anti-angiogenic, and chemosensitizing properties in a variety of cultured cells and in vivo systems. Although resveratrol is redox active and has been claimed to be an antioxidant.
Summary and conclusion
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Cancer stem cells (CSCs), a small subset of tumor cells, are characterized by self-renewing capacity, heterogeneity and resistance to several therapies (such as chemotherapy and radiotherapy), and contribute to the process of tumor development, infiltration, metastasis and recurrence. As common stem related transcription factors, octamer-binding transcription factor 4 (Oct4) and sex determining region Y-box 2 (Sox2) are considered as critical regulators of self renewal and pluripotency of embryonic stem, mediating tumor proliferation and tumor differentiation.
The chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer, being involved in chemotaxis, stemness and drug resistance.
The objective of this study was to examine the role of resveratrol as radiosensitizer by targeting CSCs in radioresistant PC-3 cell line treated with ionizing radiation by measuring gene expression of stem cell markers Sox2, Oct4 and CXCR4.
This study was an in vitro study employed the PC-3 cell line which was spilt into four groups. group I (CO): Control group composed of cells grown in the same medium without treated with ionizing radiation or resveratrol , group II (IR): Cells treated with ionizing radiation alone (exposed to various doses 2, 4, 6 and 8Gy), group III (RV): Cells treated with resveratrol alone (at the half maximal inhibitory concentration[(IC50) 140, 70 and 35μM)], group IV (IR&RV): Cells treated with different concentration of resveratrol (140, 70 and 35μM) and ionizing radiation at different doses (2,4,6,8 Gy).
Cell viability has been determined by Methyl thiazolyldiphenyl-tetrazolium assay, Stem cell markers was measured by RT-PCR and the
Summary and conclusion
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impact of IR on propagation tumor cells will be determined by Clonogenic assay.
Our results showed that:
● Ionizing radiation significantly reduced the cell viability of prostate cancer cells (PC-3) and reduced Oct4 and Sox2 genes expression at all doses (2, 4, 6 and 8 Gy) and Increased CXCR4 gene expression at all doses when compared to the untreated control group.
● Resveratrol significantly reduced the cell viability of PC-3 cell line and significantly lowered Oct4 and Sox2 genes expression at 35, 70and 140 μM . Expression of CXCR4 gene was significantly decreased when PC-3 cells were treated with resveratrol alone at IC50 (140 μM)
● Combining resveratrol and ionizing radiation leads to a significant reduction in cell viability and Oct4, Sox2 and CXCR4 genes expression especially at IC 50 (140 μM) which was noticed with increasing the radiation dose when compared to ionizing radiation alone in treated group.