Paper Information

Journal:   IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES   MAY 2013 , Volume 16 , Number 5; Page(s) 710 To 718.
 
Paper: 

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

 
 
Author(s):  ZHANG XIAOYAN, ZHAO JING, ZHU WENYAN, GOU HONGFENG, CAO DAN, YANG YU., HUANG YING*, YI CHENG*
 
* DEPARTMENT OF MEDICAL ONCOLOGY, CANCER CENTER OF WEST CHINA HOSPITAL, SICHUAN UNIVERSITY, NO.37, GUOXUEXIANG ROAD, WUHOU DISTRICT, CHENGDU 610041, SICHUAN PROVINCE, CHINA
 
Abstract: 

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.

 
Keyword(s): APOPTOSIS, CISPLATIN, DCR2, NONSMALL CELL LUNG CANCER, SUBTOXIC-DOSE, TRAIL
 
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