Fig. 8: Co-inhibition of TDP1 and DSB repair pathway enhanced cellular sensitivity to CPT treatment.

a Working model of TOP1-induced damage repair in WT and TDP1-KO cells. b The proliferation of HEK293A-WT, TDP1-KO, MUS81-KO, and MUS81/TDP1-DKO cells was measured using a CellTiter-Glo assay after 3 days in the presence of the indicated concentrations of CPT. Data are presented as the mean ± SD (n = 3 biologically independent experiments). A two-tailed unpaired t-test was used for statistical analysis of the IC50 of each cell line. **p (HEK293A-WT vs. TDP1-KO) = 0.005347, ***p (HEK293A-WT vs. MUS81-KO) = 0.000216, ****p (HEK293A-WT vs. MUS81/TDP1-DKO) = 0.000024, and ***p (TDP1-KO vs. MUS81-KO) = 0.000442. c The proliferation of HEK293A-WT and TDP1-KO cells was measured using a CellTiter-Glo assay after 7 days in the presence of the indicated concentrations of CPT and DNAPKi (AZD7648) + CPT. Data are presented as the mean ± SD (n = 3 biologically independent experiments). A two-tailed unpaired t-test was used for statistical analysis of the IC50 of each cell line. ***p (WT_CPT vs. WT_DNAPKi+CPT) = 0.000276, **p (WT_CPT vs. TDP1-KO_CPT) = 0.001041, and ***p (WT_CPT vs. TDP1-KO_DNAPKi + CPT) = 0.000685. d The proliferation of HEK293A-WT and TDP1-KO cells was measured using a CellTiter-Glo assay after 7 days in the presence of the indicated concentrations of CPT and ATMi (KU55933) + CPT. Data are presented as the mean ± SD (n = 3 biologically independent experiments). A two-tailed unpaired t-test was used for statistical analysis of the IC50 of each cell line. **p (WT_CPT vs. WT_ATMi+CPT) = 0.001008, **p (WT_CPT vs. TDP1-KO_CPT) = 0.001041, and ***p (WT_CPT vs. TDP1-KO_ATMi+CPT) = 0.000859.