Synergistic Effect of Subtoxic-dose Cisplatin and TRAIL to Mediate Apoptosis by Down-regulating Decoy Receptor ۲ and Up-regulating Caspase-۸, Caspase-۹ and Bax Expression on NCI-H۴۶۰ and A۵۴۹ Cells
- سال انتشار: 1392
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 16، شماره: 5
- کد COI اختصاصی: JR_IJBMS-16-5_009
- زبان مقاله: انگلیسی
- تعداد مشاهده: 167
نویسندگان
۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei Province, China
۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
۲Department of Pathophysiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan Province, China
۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
چکیده
Objective(s): Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells, more than half of tumors including non-small cell lung cancer (NSCLC) exhibit TRAIL-resistance. The purpose of this study was to determine whether subtoxic-dose cisplatin and TRAIL could synergistically enhance apoptosis on NSCLC cells and investigate its underlying mechanisms. Materials and Methods:NCI-H۴۶۰ and A۵۴۹ cells were treated with TRAIL alone, cisplatin alone or combination treatment in this study. The cytotoxicity was evaluated according to Sulforhodamine B assay, and apoptosis was examined using Hoechst ۳۳۳۴۲ staining and flow cytometry. The mRNA and protein levels of TRAIL receptors and apoptotic proteins including caspase-۸, caspase-۹, Bcl-۲ and Bax were determined by RT-PCR and Western blotting, respectively. Results:Our results showed that NCI-H۴۶۰ cells were sensitive to TRAIL, whereas A۵۴۹ cells were resistant. However, subtoxic-dose cisplatin could enhance the both cells to TRAIL-mediated cell proliferation inhibition and apoptosis. The underlying mechanisms might be associated with the down-regulation of DcR۲ and up-regulation of Caspase-۸, Caspase-۹ and Bax. Conclusion:Subtoxic-dose cisplatin could enhance both TRAIL- sensitive and TRAIL- resistant NSCLC cells to TRAIL-mediated apoptosis. These findings motivated further studies to evaluate such a combinatory therapeutic strategy against NSCLC in the animal models.کلیدواژه ها
Apoptosis Cisplatin DcR۲ Nonsmall cell lung cancer Subtoxic-dose TRAILاطلاعات بیشتر در مورد COI
COI مخفف عبارت CIVILICA Object Identifier به معنی شناسه سیویلیکا برای اسناد است. COI کدی است که مطابق محل انتشار، به مقالات کنفرانسها و ژورنالهای داخل کشور به هنگام نمایه سازی بر روی پایگاه استنادی سیویلیکا اختصاص می یابد.
کد COI به مفهوم کد ملی اسناد نمایه شده در سیویلیکا است و کدی یکتا و ثابت است و به همین دلیل همواره قابلیت استناد و پیگیری دارد.