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. Author manuscript; available in PMC: 2020 Jul 30.
Published in final edited form as: Cell Rep. 2020 Jul 14;32(2):107884. doi: 10.1016/j.celrep.2020.107884

Figure 6. CDK7 Inhibitor THZ1 Acts Synergistically with PARP Inhibition in HR-Proficient Cancer Cells.

Figure 6.

(A and B) Sensitivity of MDA-MB-231, MDA-MB-468, OVCAR5, OVCAR3, DU145, and PC3 cells to olaparib alone or olaparib combined with low-dose THZ1 (12.5 nM and 25 nM or 50 nM) by cell viability assay; 1,000 cells were seeded in 96-well plates and treated with different concentration of inhibitors for 3 days. Survival fraction (A) and the combination index (B) are shown for each of the cell lines, respectively. Fa, fraction affected. Data represented as means ± SD, n = 3 biological replicates, *p < 0.05 determined by two-tailed Student’s t test.

(C) Crystal-violet staining of MDA-MB-231, OVCAR5, and DU145 cells treated with different conditions.

(D) Anchorage-independent soft agar assay results for MDA-MB-231, OVCAR5, and DU145 cells treated with DMSO, THZ1, olaparib, or olaparib combined with THZ1. Crystal violet staining (left) and its quantification (right) were shown for the above lines. Data represented as means ± SD, n = 3 biological replicates, *p < 0.05 determined by two-tailed Student’s t test.

(E) Schematic illustrating the MDA-MB-231 mouse xenograft experimental design. MDA-MB-231 cells were implanted subcutaneously in mice and grown until tumors reached a size of approximately 30 mm3. Xenografted mice were randomized and then received vehicle, 10 mg kg−1 THZ1, 50 mg kg−1 olaparib, or the combination of both agents, as indicated, 5 days/week for 4 weeks. Caliper measurements were taken every other day from the initiation of drug treatment.

(F) Mean tumor volume is shown; n = 10 mice/group. Statistical analysis by two-tailed Student’s t test. Error bars represent means ± SD.

(G) Images of tumors collected from animals receiving vehicle, THZ1, olaparib, or the combination of both agents.

(H) Individual tumor weights from different treatment groups are shown. Statistical analysis by two-tailed Student’s t test. Error bars represent means ± SD.

(I) Schematic illustrating the OVCAR5 mouse xenograft experimental design. OVCAR5 cells were implanted subcutaneously in mice and grown until tumors reached a size of approximately 30 mm3. Xenografted mice were randomized and then received vehicle, 10 mg kg−1 THZ1, 50 mg kg−1 olaparib, or the combination of both agents, as indicated, 5 days/week for 3 weeks. Caliper measurements were taken every other day from the initiation of drug treatment.

(J) Mean tumor volume is shown; n = 8 mice/group. Statistical analysis by two-tailed Student’s t test. Error bars represent means ± SD.

(K) Images of tumors collected from animals receiving vehicle, THZ1, olaparib, or the combination of both agents.

(L) Individual tumor weights from different treatment groups are shown. Statistical analysis by two-tailed Student’s t test. Error bars represent means ± SD.