| چکیده انگلیسی مقاله |
Objective(s): Classical Hodgkin lymphoma (cHL) is identified by the appearance of Hodgkin and Reed-Sternberg cells. A20 and CYLD are deubiquitinating enzymes involved in negatively regulating NF-κB-mediated immune response. Vincristine (Vinc) and doxorubicin (Dox) are classical antitumor drugs, in which Dox serves a key role in chemotherapy against cHL and Vinc induces disruption of microtubule function that inhibits mitosis of cancer cells. Little is known about the roles of A20/CYLD in regulating macrophage function from cHL patients upon treatment with Vinc or Dox. This study, therefore, asked whether A20/CYLD expression affects function of macrophages in cHL cases. Materials and Methods: Macrophages from cHL patients differentiated from bone marrow cells were exposed to Vinc or Dox. Gene expression levels were determined by real time-qPCR, cell maturation, apoptosis and phagocytosis by flow cytometry, and cytokine release by ELISA. Results: Dox induced maturation, apoptosis, and phagocytosis of macrophages in cHL cases. Moreover, the percentage of CD68+CD40+, but not CD68+CD86+ cells as well as levels of IL-1β were further enhanced when exposed to A20 siRNA, whereas the absence of CYLD unaltered macrophage function in cHL patients. Importantly, the increased numbers of A20-sensitive CD68+CD40+ and Annexin V-PI+ cells as well as enhanced levels of caspase 3 were abolished in the presence of mTOR inhibitor Everolimus. Conclusion: The present study indicates that Dox-induced macrophage maturation and apoptosis are dependent on A20 expression through mTOR signaling. Moreover, inhibition of Dox-induced macrophage maturation in the patients with low A20 expression by Everolimus might represent a promising therapy for A20-sensitive cHL cases. |
| نویسندگان مقاله |
| Nguyen Canh
Faculty of Biotechnology, Vietnam National University of Agriculture, Hanoi, Vietnam
| Phan Trang
Military Hospital 103, Vietnam Military Medical University, Phung Hung, Ha Dong, Hanoi, Vietnam|Department of Pathophysiology, Vietnam Military Medical University, Phung Hung, Ha Dong, Hanoi, Vietnam
| Pham Huong
Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam
| Do Thi Trang
Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam|Publishing House for Science Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, HaNoi, VietNam
| Pham Nhat
Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam
| Nguyen Manh
Department of Military Epidemiology, Vietnam Military Medical University, Phung Hung, Ha Dong, Hanoi, Vietnam
| Le Thanh
108 Military Central Hospital, Tran Hung Dao, Hai Ba Trung, Hanoi, Vietnam
| Nguyen Nam
Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam
| Nguyen Vuong
Military Hospital 103, Vietnam Military Medical University, Phung Hung, Ha Dong, Hanoi, Vietnam
| Nguyen Xuan
Institute of Biology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam
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