Original Article DNA microarray reveals different pathways responding to paclitaxel and docetaxel in non-small cell lung cancer cell line

Chun-Li Che, Yi-Mei Zhang, Hai-Hong Zhang, Yu-Lan Sang, Ben Lu, Fu-Shi Dong, Li-Juan Zhang, Fu-Zhen Lv
2013 Int J Clin Exp Pathol   unpublished
The wide use of paclitaxel and docetaxel in NSCLC clinical treatment makes it necessary to find biomark-ers 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
more » ... nse 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 ki-nases (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 cycleregulation (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. Inroduction Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all cases of lung cancer [1], the leading cause of cancer-related death in both men and women in the world. Unfortunately, at the time of diagnosis, the majority of patients already have locally advanced or metastatic disease and a system-ic, palliative treatment is one of few therapeutic options. Paclitaxel alone or combination with carboplat-in has been approved by FDA to treat advanced or metastatic NSCLC. Docetaxel, the second taxoid derivative, has also shown anti-tumor activity in NSCLC, and numerous clinical trials evaluating the therapeutic effect of docetaxel on NSCLC patients are ongoing (http://www. clinicaltrials.gov/). Actually, cisplatin with docetaxel is one of the most commonly used regimens to treat advanced NSCLC in the UK [2]. Several large clinical trials have shown that, when combined with cisplatin or carboplatin, paclitaxel has similar activity and efficacy with docetaxel, either one offered a significant advantage over another for advanced NSCLC [3-6]. The response rate of paclitaxel or docetaxel-based combination regimens is 16-24% [7], which means that most advanced NSCLC patients do not respond to these che-motherapies. Patients that respond to one of these regimens may also respond to another one: such crossover effects provide evidence of heterogeneity of chemosensitivity in NSCLC [2,