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International Journal of Hematology-Oncology and Stem Cell Research، جلد ۱۱، شماره ۲، صفحات ۱۴۸-۱۵۷
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عنوان انگلیسی Anti-Apoptotic Effects of Osteopontin via the Up-Regulation of AKT/mTOR/β-Catenin Loop in Acute Myeloid Leukemia Cells
چکیده انگلیسی مقاله Background: The conventional chemotherapeutic regimens which applied for treatment of acute myeloid leukemia (AML) mostly target tumor bulk but not leukemic stem cells (LSCs). Aberrant expression or activation of mediators such as osteopontin (OPN) or PI3K/PTEN/Akt/mTOR pathway plays a key role in making prone to develop leukemia. Preventing or treating cancer by curcumin (CUR) has been suggested recently. CUR induces apoptosis and growth inhibition through various mechanisms in leukemic cells. In present study, we tried to measure the toxic response in vitro to CUR for evaluation of changes in cell viability, survival and molecular-mediated resistance in primary AML cells. Materials and Methods: Isolated primary CD34+/CD38− bone marrow derived AML cells were treated with CUR, Daunorubicin (DNR) and/or their combination by MTT assay, Annexin V/PI staining, and colony-formation. The mRNA expression of OPN/AKT/mTOR/PTEN/β-catenin genes was measured by Real-Time PCR. The siRNA against OPN was applied for CUR- treated cells. Results: Growth inhibition effect of DNR increased in combination with CUR on primary CD34+/CD38- AML cells. Suppression of OPN with siRNA increased the cytotoxic effects of CUR. Likewise, OPN gene expression increased in response to CUR treatment in AML cells. AKT, mTOR, β-catenin or PTEN gene expression increased by CUR, but OPN siRNA decreased the level of mRNA expression of mentioned molecular pathway. Conclusion: The chemo-resistance of AML cells against therapy might be relevant to increasing of OPN mRNA expression and activity of other mediators including AKT, mTOR, PTEN, and β-catenin. In this context, targeting of OPN might be more impact on CD34+ AML cells.
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نویسندگان مقاله | Mahdi Zahed Panah
Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran


| Mohsen Nikbakht
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran


| Seyed Mehdi Sajjadi
Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran


| Shahrbano Rostami
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran


| Amir Hossein Norooznezhad
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran


| Hosein Kamranzadeh Fumani
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran


| Ardeshir Ghavamzadeh
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran


| Saeed Mohammadi
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
نشانی اینترنتی http://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/645
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