Expression profile of apoptosis related genes and radio-sensitivity of prostate cancer cells

Abstract

Radio-resistant or recurrent prostate cancer represents a serious health risk for approximately 20%-30% of patients treated with primary radiation therapy for clinically localized prostate cancer. In the present study, we investigated the expression profiles of 84 genes involved in various apoptosis pathways in two prostate cancer cell lines LNCaP (P53+ and AR+) and PC3 (P53- and AR-). We also studied the effect of monensin, an apoptosis inducing reagent, in X-ray-induced cell killing. Comparison of gene expressions between unirradiated LNCaP and PC3 cells revealed distinguished gene expression patterns. The data showed a significantly higher expression level of genes involved in the caspase/card family and the TNF ligand/receptor family in PC3 cells, whereas, LNCaP cells exhibited higher expressions in the p53 related genes. At 2 and 4 hrs post a 10 Gy X-ray exposure, changes of gene expressions were detected in a significant fraction of the genes in LNCaP cells, but no significant changes were found in PC3 cells. There was no significant apoptosis-inducing effect of X-rays (up to 10 Gy) in both cell lines; however, monensin was shown to be effective in inducing apoptosis in LNCaP, but not in PC3 cells. In addition, the effect of combined treatment of monensin and X-rays in LNCaP cells appeared to be synergistic. Our results suggest that monensin may be effective for both cancer cell killing and radiosensitizing, and the different expression profiles in apoptosis related genes in cancer cells may be correlated with their sensitivity to apoptosis inducing reagents.