TP53 wild type cells are resistant to arsenic trioxide induced dynamic transcriptional changes

Previous and our results show that cells with mutant p53 are more sensitive to arsenic trioxide (ATO) induced cell growth inhibition. To explore the underling mechanisms, we conduct a detailed analysis of the globe transcriptional profiles of ATO regulated genes in breast, colon and lung cancer cells with different p53 status. We find p53 wild type cells are resistant to ATO induced globe dynamic transcriptional changes, thus resistant to ATO induced cell growth inhibition. P53 inhibitor PFTα releases p53 mediated transcriptional resistance and increases the sensitivity of ATO in p53 wild type tumor cells. Breast cancer SKBR3, MCF7, colon cancer SW620, HCT116 and lung cancer H1299, A549 cells were treated with ATO 5μM for 0, 6, 12, 24 and 36 hours. TP53 wild type MCF7, HCT116 and A549 cells were treated with the combination of ATO and TP53 inhibitor PFTα at 6h, 12h, 24h and 36 hours. Total RNA was collected and profiled to Affymetrix microarray.