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Iranian Biomedical Journal، جلد ۲۳، شماره ۵، صفحات ۳۱۲-۳۲۳
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عنوان انگلیسی Novel Poly(Adenosine Diphosphate-Ribose) Polymerase (PARP) Inhibitor, AZD2461, Down-Regulates VEGF and Induces Apoptosis in Prostate Cancer Cells
چکیده انگلیسی مقاله Background: Prostate cancer (Pca) is a heterogeneous disease, and current treatments are not based on molecular stratification. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have recently been found to be remarkably toxic to cells with defects in homologous recombination, particularly cells with BRCA-mutated backgrounds. Therefore, this preliminary study was designed to evaluate whether PTEN expression status could have an impact on the sensitivity of invasive Pca cells to the PARP inhibitor, AZD2461. Methods: MTT viability test, Annexin V‐FITC/propidium iodide double staining, and caspase3 activity assay were used to evaluate the apoptosis and relative expression of PTEN and VEGF in PC-3 and DU145 cell lines using real-time PCR. Results: MTT results showed that the inhibitory effects of AZD2461 were higher in PC-3 than DU145 cells (with IC50 of 36.48 and 59.03 µM at 48 hours of treatment, respectively). Flow cytometric analysis also showed the same results. When exposed to 40 µM of AZD2461, PC-3 (38.8%) and DU145 (28%) cells underwent apoptosis (p < 0.05). Treatment of cells by AZD2461 also caused a significant increase in apoptosis through caspase3 activation in both cell lines. VEGF mRNA levels in PC-3 cells significantly decreased compared to adjusted untreated cells (p < 0.05) in all measured times while displaying different alteration patterns in DU145 cells (p < 0.05). Conclusion: AZD2461 suppresses the growth of prostate tumor cells since AZD2461 monotherapy could prove to be efficacious, especially against cells not expressing PTEN besides activating the possible apoptosis-independent cell death pathways.
کلیدواژه‌های انگلیسی مقاله AZD2461, DNA repair, PARP, Prostate neoplasm
نویسندگان مقاله | Saman Sargazi
International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran,


| Ramin Saravani
Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran


| Javad Zavar Reza
Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Science, Yazd, Iran,


| Hossein Zarei Jaliani
Protein Engineering Laboratory, Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran


| Hamidreza Galavi
Cellular and Molecular Research Center of Zahedan University of Medical Sciences, Zahedan, Iran,


| Mahdiyeh Moudi
Genetics of Non-Communicable Disease Research Center of Zahedan University of Medical Sciences, Zahedan, Iran


| Najmeh Alsadat Abtahi
International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
نشانی اینترنتی http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-1-764&slc_lang=en&sid=1
فایل مقاله اشکال در دسترسی به فایل - ./files/site1/rds_journals/125/article-125-1687390.pdf
کد مقاله (doi)
زبان مقاله منتشر شده en
موضوعات مقاله منتشر شده Cancer Biology
نوع مقاله منتشر شده مقاله کامل
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