Ailanthone inhibits non-small cell lung cancer cell growth through repressing DNA replication via downregulating RPA1

Abstract

Background:The identification of bioactive compounds from Chinese medicine plays a crucial role in the development of novel reagents against non-small lung cancer (NSCLC).Methods:High throughput screening assay and analyses of cell growth, cell cycle, apoptosis, cDNA microarray, BrdU incorporation and gene expression were performed.Results:Ailanthone (Aila) suppressed NSCLC cell growth and colony formation in vitro and inhibited NSCLC tumour growth in subcutaneously xenografted and orthotopic lung tumour models, leading to prolonged survival of tumour-bearing mice. Moreover, Aila induced cell cycle arrest in a dose-independent manner but did not induce apoptosis in all NSCLC cells. Furthermore, 1222 genes were differentially expressed upon Aila administration, which were involved in 21 signal pathways, such as DNA replication. In addition, Aila dose-dependently decreased BrdU incorporation and downregulated the expression of replication protein A1 (RPA1).Conclusions:Aila inhibited the growth of NSCLC cells through the repression of DNA replication via downregulating RPA1, rather than through cell cycle arrest and apoptosis. Our findings suggested that Aila could be used as a promising therapeutic candidate for NSCLC patients.