Xiaoyan Zhang - ۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
Jing Zhao - Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei Province, China
Wenyan Zhu - ۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
Hongfeng Gou - ۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
Dan Cao - ۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
Yu Yang - ۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
Ying Huang - ۲Department of Pathophysiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan Province, China
Cheng Yi - ۱Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

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.

Apoptosis Cisplatin DcR۲ Nonsmall cell lung cancer Subtoxic-dose TRAIL