Poly ADP-ribose Polymerase(PARP) Inhibitor AG014699 Improve Radiosensitivity Of BRCA2 Deficient Pancreatic Cancer Cells In Vitro Experimental Study

Objective:Pancreatic cancer is a common gastrointestinal cancer in clinical, the prognosis is poor, and radiation therapy is an important method for the treatment of pancreatic cancer, the paper discusses the AG014699 improve BRCA2 defects of pancreatic cancer CAPAN-1 cells radiosensitization in vitro;Methods:Culturing human pancreatic cancer CAPAN-1 cells in vitro, we use the logarithmic growth phase cells for experimental study, though cell growth inhibition assay(MTT method) cells measured IC50 values. The CAPAN-1 cells were used as the control group, drug alone group, radiotherapy alone group, the drug combined with radiotherapy group, using cell cloning experiments to observe the cells cloning efficiency, analysis of cell survival state, at the same time observe the formation of H2AÑ…using immunofluorescence, then discusses molecular mechanism of radiosensi-tization;The results:(1)CAPAN-1 cell grow slowly,doubling time is long, 24-48 h in the logarithmic growth phase, 48-72 h in growth inhibition period, after at plateau;(2)at 24 h, 48 h, 72 h,using different drugs gradient AG-014699 on pancreatic cancer CAPAN-1 cells and found that CAPAN-1 with creased drug concentration,prolonged duration,inhibiting cell proliferation is enhancing(p <0.05, while CAPAN-1 cell of inhibition cell proliferation in 48 h is obvious, the IC50 values is10 umol / L;(3)Pancreatic cancer CAPAN-1 cells in the same period of the four groups in molecular cell clone was found that the number of cell clones drug combined with radiation group reduces significantly than radiotherapy alone or drug alone group(p<0.05), and then prompts AG014699 increase CAPAN-1 cells radiosensitivity;(4)radiotherapy(2Gy) and drugs combined with radiotherapy(2Gy) after 24 h,the drug combined with radiation group mitotic crisis significantly increased compared with radiotherapy alone(p <0.05).DNA damage manifested as H2 A Ñ…form, suggesting that DNA double-strand breaks are the main mode of cell death;Conclusion:AG014699 can improve human pancreatic carcinoma BRCA2 deficient of CAPAN-1 cell radiosensitivity;...