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Iranian Journal of Basic Medical Sciences، جلد ۱۶، شماره ۵، صفحات ۷۱۰-۷۱۸
عنوان فارسی
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عنوان انگلیسی Synergistic Effect of Subtoxic-dose Cisplatin and TRAIL to Mediate Apoptosis by Down-regulating Decoy Receptor 2 and Up-regulating Caspase-8, Caspase-9 and Bax Expression on NCI-H460 and A549 Cells
چکیده انگلیسی مقاله 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-H460 and A549 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 33342 staining and flow cytometry. The mRNA and protein levels of TRAIL receptors and apoptotic proteins including caspase-8, caspase-9, Bcl-2 and Bax were determined by RT-PCR and Western blotting, respectively. Results:Our results showed that NCI-H460 cells were sensitive to TRAIL, whereas A549 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 DcR2 and up-regulation of Caspase-8, Caspase-9 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.
کلیدواژه‌های انگلیسی مقاله
نویسندگان مقاله xiaoyan زانگ | xiaoyan zhang
1department of medical oncology, cancer center of west china hospital, sichuan university, chengdu, sichuan province, china


جینگ zhao | jing zhao
department of oncology, hebei general hospital, shijiazhuang, hebei province, china


wenyan zhu | wenyan zhu
1department of medical oncology, cancer center of west china hospital, sichuan university, chengdu, sichuan province, china


hongfeng gou | hongfeng gou
1department of medical oncology, cancer center of west china hospital, sichuan university, chengdu, sichuan province, china


دان cao | dan cao
1department of medical oncology, cancer center of west china hospital, sichuan university, chengdu, sichuan province, china


yu یانگ | yu yang
1department of medical oncology, cancer center of west china hospital, sichuan university, chengdu, sichuan province, china


ying هوانگ | ying huang
2department of pathophysiology, west china school of preclinical and forensic medicine, sichuan university, chengdu, sichuan province, china


چنگ yi | cheng yi
1department of medical oncology, cancer center of west china hospital, sichuan university, chengdu, sichuan province, china
نشانی اینترنتی http://ijbms.mums.ac.ir/article_785.html
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زبان مقاله منتشر شده en
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نوع مقاله منتشر شده Original Article
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