DNA microarray reveals different pathways responding to paclitaxel and docetaxel in non-small cell lung cancer cell line.
The wide use of paclitaxel and docetaxel in NSCLC clinical treatment makes it necessary to find biomarkers for identifying patients who can benefit from paclitaxel or docetaxel. In present study, NCI-H460, a NSCLC cell line with different sensitivity to paclitaxel and docetaxel, was applied to DNA microarray expression profiling analysis at different time points of lower dose treatment with paclitaxel or docetaxel. And the complex signaling pathways regulating the drug response were identified, and several novel sensitivity-realted markers were biocomputated.The dynamic changes of responding genes showed that paclitaxel effect is acute but that of docetaxel is durable at least for 48 hours in NCI-H460 cells. Functional annotation of the genes with altered expression showed that genes/pathways responding to these two drugs were dramatically different. Gene expression changes induced by paclitaxel treatment were mainly enriched in actin cytoskeleton (ACTC1, MYL2 and MYH2), tyrosine-protein kinases (ERRB4, KIT and TIE1) and focal adhesion pathway (MYL2, IGF1 and FLT1), while the expression alterations responding to docetaxel were highly co-related to cell surface receptor linked signal transduction (SHH, DRD5 and ADM2), cytokine-cytokine receptor interaction (IL1A and IL6) and cell cycle regulation (CCNB1, CCNE2 and PCNA). Moreover, we also confirmed some different expression patterns with real time PCR. Our study will provide the potential biomarkers for paclitaxel and docetaxel-selection therapy in clinical application.
Department of respiratory medicine, First Clinical Medical College affiliated to Harbin Medical University, Harbin, China.
Chun-Li
CL
Che
Yi-Mei
YM
Zhang
Hai-Hong
HH
Zhang
Yu-Lan
YL
Sang
Ben
B
Lu
Fu-Shi
FS
Dong
Li-Juan
LJ
Zhang
Fu-Zhen
FZ
Lv
D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D043823:Taxoids / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel
Non-small cell lung cancer; docetaxel; microarray; paclitaxel