AZT-mediated inhibition of telomerase activity suppresses pancreatic cancer cell proliferation and enhances their radiosensitivity

Objective: To investigate the effects of AZT-mediated inhibition of telomerase activity on the proliferation, apoptosis and radiosensitivity of panc1 cells, and the growth of pancreatic tumor in vivo. Methods: panc1 cells were divided into four groups: A, control group; B, 0.4 mmol/L AZT; C, 0.6 mmol/L AZT; and D, 0.8 mmol/L AZT group. Cell proliferation was assessed by MTT assay. Cell apoptosis was detected by flow cytometry. Telomerase activity was measured by the quantitative TRAP-ELISA and the level of hTERT mRNA expression was determined by RT-PCR analysis. The changes in the radiosensitivity of cells were analyzed by colony formation assay and cell survival curve. Further, a xenograft mouse model of human pancreatic cancer was constructed and the effect of AZT-mediated telomerase activity on the tumor growth in vivo was evaluated. Results: Telomerase activity in group B, C and D was decreased by 8.4%, 14.6% and 24%, respectively compared with the control group. The expression of hTERT mRNA in group B, C and D was significantly decreased (P < 0.05). ATZ significantly reduced the cell viability in group B, C and D (P < 0.05), but significantly increased the percentage of early apoptotic cells in the three groups in a dosedependent manner (P < 0.05). Moreover, ATZ dose-dependently increased the radiosensitivity of cells in group B, C and D compared with the control group. In animal studies, the tumor volume of nude mice in AZT, radiation and the combination group of AZT and radiation was decreased compared with the blank control, whereas the tumor volume in the combination group was significantly smaller than that in the other two treatment groups (P < 0.05). Conclusion: AZT-mediated inhibition of telomerase activity suppresses the proliferation of pan1 cells, induces their apoptosis, increases their radiosensitivity, and inhibits the growth of pancreatic tumor in vivo.