Role of DNA-PK dependent NHEJ and PARP dependent BER on sensitivity of glioma cells knockdown for Rad51 towards TMZ.

<p>(<b>A</b>) Inhibition of DNA-PK activity with NU7026. DNA-PK activity was determined in cell extracts in the presence and absence of NU7026. (<b>B</b>) Clonogenic survival of stable Rad51 knocked-down glioma cells (LN-229-Rad51sh-4) compared to empty vector-transfected cells (LN-229-pS-empty) after TMZ or ionizing radiation (IR) treatment in the presence or absence of the DNA-PKcs inhibitor NU7026. Equitoxic TMZ and ionizing radiation (IR) doses producing about 30 to 40% toxicity in the absence of DNA-PK inhibition were used [TMZ/IR doses: LN-229-pS-empty: 2.7 µM/2.7Gy; LN-229-Rad51sh-4: 1.5 µM/1.9 Gy]. *, p<0.05, significance levels were calculated using the Mann-Whitney U test (n = 5). (<b>C</b>) Clonogenic survival of control (LN-229-pS-empty-2) and Rad51 knockdown (LN-229-Rad51sh-23) glioma cells as a function of olaparib concentration. Cells were co-treated with TMZ or not. TMZ doses producing 30 to 40% toxicity in the absence of PARP inhibition were selected for LN-229-Rad51sh-23 (0.8 µM) and control cells (2.5 µM).