In vitro study | In response to XRT and gemcitabine, VE-822(80 nM) attenuates the ATR signaling pathway and decreases tumor cell survival. In normal cells, VE-822(80 nM) attenuated the intensity of the ATR signaling pathway, but did not enhance the ability of radiation and gemcitabine to kill normal cells. VE-822(80 nM) increased residual γH2AX and 53BP1 foci elicited by XRT compared to MiaPaCa-2 and PSN-1 cells in XRT. MiaPaCa-2 and PSN-1 cells in the XRT, VE-822(80 nM) were treated before reducing the focus of RAD51. VE-822(80 nM) alone increased the rate at which MiaPaCa-2 and PSN-1 cells stayed in the G1 phase. VE-822(80 nM) reduces XRT-enriched G2/M-phase-fraction in MiaPaCa-2 and PSN-1 cells. VE-822 alone had little effect, while VE-822(80 nM),XRT and/or gemcitabine and combination enhanced early and late apoptosis in PSN-1 cells. VE-822 increased tumor response to DNA damaging agents and was associated with pChk1 Ser345 obstruction. |