XIAP-mediated protection of H460 lung cancer cells against cisplatin.
Molecular mechanism(s) responsible for drug resistance of non-small cell lung cancer (NSCLC) cells to cisplatin was investigated. Results showed that cisplatin (50muM)-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).
Cheng
Yow-Jyun
YJ
Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
Jiang
Hang-Shiang
HS
Hsu
Shih-Lan
SL
Lin
Li-Chiung
LC
Wu
Chieh-Liang
CL
Ghanta
Vithal K
VK
Hsueh
Chi-Mei
CM
D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013997:Time Factors; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D016227:Benzoquinones; D034741:RNA, Small Interfering; D051636:X-Linked Inhibitor of Apoptosis Protein; D045304:Cytochromes c; D053148:Caspase 3; D002945:Cisplatin; C010945:embelin