ABSTRACT
Docetaxel has been used as first-line chemotherapy in advanced non-small cell lung carcinoma (NSCLC), but further extensive and effective application is prevented by drug resistance. MicroRNAs (miRNAs) have recently been identified as important posttranscriptional regulators, which are involved in various biological processes. The aim of this study was to identify microRNA expression profiles involved in the development of docetaxel resistance in NSCLC. Here, microarray chip technology was employed to identify miRNA expression profiles in docetaxel-resistant human NSCLC cell line (SPC-A1/docetaxel). Then, the changes of miRNAs expression (>2-fold compared with control SPC-A1 cell line) were testified by quantitative real-time RT-PCR (qRT-PCR) assay. Furthermore, the potential target genes regulated by selected miRNAs were analysed by various target prediction tools. The expression of a total of 52 miRNAs showed significant difference between SPC-A1/docetaxel cells and control SPC-A1 cells (P < 0.01). Six miRNAs (miR-192, 200b, 194, 424, 98 and 212) exhibited more than 2-fold changes in their expression levels, which were validated by qRT-PCR. The expression of three miRNAs (miR-200b, 194 and 212) was significantly down-regulated in SPC-A1/docetaxel cells, while the expression of other three miRNAs (miR-192, 424 and 98) was significantly up-regulated in SPC-A1/docetaxel cells (P < 0.01). Potential target genes controlled by six selected miRNAs were divided into four groups according to various functions: apoptosis and proliferation (71 genes), cell cycle (68 genes), DNA damage (26 genes) and DNA repair (59 genes). The expression of a few target genes in SPC-A1/docetaxel and SPC-A1 cells were further confirmed by qRT-PCR and Western blot. Taken together, the identification of microRNA expression profiles in docetaxel-resistant NSCLC cells could provide a better understanding of mechanisms involved in drug sensitivity or resistance, which would be helpful to develop novel strategies for targeted therapies in chemorefractive NSCLC patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung , Drug Resistance, Neoplasm/genetics , Lung Neoplasms , MicroRNAs/metabolism , Taxoids/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/physiopathology , Cell Line, Tumor , Docetaxel , Gene Expression Profiling , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/physiopathology , MicroRNAs/genetics , Microarray AnalysisABSTRACT
Prostate cancer is one of the most common type of cancer among men after middle age. Androgen withdrawal can delay its progression in the initial stage, but it finally becomes independent of androgens in almost all the cases. The combination of docetaxel with prednisone is currently a standard first-line treatment for patients with hormone-refractory prostate cancer (HRPC), but hitherto there is no established second-line therapy. In view of the molecular pathogenesis of HRPC, this article presents an overview on several promising drugs that target specific pathways, involving angiogenesis, cell signaling, apoptosis and proliferation, and immune modulation, either as single agents or in combination with cytotoxic chemotherapy.
Subject(s)
Humans , Male , Drug Resistance, Neoplasm , Hormones , Pharmacology , Prostatic Neoplasms , Drug TherapyABSTRACT
In China, the incidence of prostate cancer has been increasing in recent years. Hormonal therapy has been the mainstay of the therapeutic options for metastatic diseases for many years. But many metastatic tumors progress at a median of two to five years and become hormonal refractory prostate cancer (HRPC). This article summarizes in the advances of diagnostic criteria, molecular biological features, prediction markers, new therapeutic agents and further researches to be undertaken concerning HRPC.
