XIAP-mediated protection of H460 lung cancer cells against cisplatin

• Published in: European journal of pharmacology 2010-02, Vol.627 (1), p.75-84
• Main Authors: Cheng, Yow-Jyun, Jiang, Hang-Shiang, Hsu, Shih-Lan, Lin, Li-Chiung, Wu, Chieh-Liang, Ghanta, Vithal K., Hsueh, Chi-Mei
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Benzoquinones - pharmacology; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - pathology; Caspase 3; Caspase 3 - metabolism; Cell Line, Tumor; Cisplatin; Cisplatin - pharmacology; Cytochromes c - metabolism; Dose-Response Relationship, Drug; Drug resistance; Drug Resistance, Neoplasm - drug effects; Gene Knockdown Techniques; Humans; Lung Neoplasms - pathology; Medical sciences; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondria - metabolism; NSCLC; Pharmacology. Drug treatments; Pneumology; RNA, Small Interfering - genetics; Time Factors; Tumors of the respiratory system and mediastinum; X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors; X-Linked Inhibitor of Apoptosis Protein - deficiency; X-Linked Inhibitor of Apoptosis Protein - genetics; X-Linked Inhibitor of Apoptosis Protein - metabolism; XIAP
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2009.11.003

Molecular mechanism(s) responsible for drug resistance of non-small cell lung cancer (NSCLC) cells to cisplatin was investigated. Results showed that cisplatin (50 μM)-induced cell death (apoptosis) was more significant in CH27 and A549 cell lines than in H460. The high protein levels of X-linked inhibitor-of-apoptosis protein (XIAP) observed in H460 cells appeared to play a key role in the regulation of cisplatin resistance of H460 cells. XIAP can bind to and suppress the activities of caspase 3 in H460 cells and lead to apoptosis inhibition of these cells. Blockade of XIAP activity by Embelin (XIAP inhibitor) or siRNA has increased caspase 3 activities and promoted cisplatin-induced cell death of H460 cells. The results indicate a therapeutic value of Embelin and/or XIAP siRNA in the control of cisplatin-resistant NSCLC cells (H460).