Skip to main content
Fig. 6 | Molecular Cancer

Fig. 6

From: CDK9 inhibition induces epigenetic reprogramming revealing strategies to circumvent resistance in lymphoma

Fig. 6

Combination strategies to overcome resistance to CDK9i. A DLBCL cell lines were treated with the CDK9 inhibitor AZD4573 and/or the PIM family inhibitor AZD1208, or the PIM1 inhibitor SGI1776, as single agents or in combination at the indicated doses for 48 h. Proliferation was analyzed using a colorimetric tetrazolium-based assay. Data is shown as mean ± SEM of three independent experiments. *p < 0.05 and **p < 0.01 vs. untreated control unless otherwise notated. B Primary MCL cells were co-cultured with CD40 ligand expressing stroma for 24 h then were treated with AZD4573, AZD1208, or SGI1776 as single agents or in combination for 48 h. Apoptosis was determined by flow cytometry using Annexin-V-FITC staining. Data is from three patient samples. *p < 0.05 and **p < 0.01. C DLBCL cell lines were treated with the CDK9 inhibitor AZD4573 (3 nM) and/or the PI3K inhibitor AZD8835 (100 nM) as single agents or in combination for 48 h. Proliferation was analyzed using a colorimetric tetrazolium-based assay. Data is shown as mean ± SEM of three independent experiments. *p < 0.05 and **p < 0.01 vs. untreated control unless otherwise notated. D Primary MCL cells were co-cultured with CD40 ligand expressing stroma for 24 h then were treated with the CDK9 inhibitor AZD4573 or the PI3K inhibitor AZD8835 as single agents or in combination for 48 h. Apoptosis was determined by flow cytometry using Annexin-V-FITC staining. Data is from five patient samples. *p < 0.05 and **p < 0.01. E–F Mice were inoculated with OCI-LY3 cells as described in the methods. Once tumor volume reached 100 mm3, mice began treatment with AZD4573 (15 mg/kg; IP; once weekly), copanlisib (15 mg/kg; IP; twice weekly), a combination of both, or vehicle control. E Tumor growth starting from the first day of engraftment is shown. Data is represented as mean ± SEM of 10 tumors. *p < 0.05 and **p < 0.01, combo treatment versus control. F Kaplan–Meier survival curve is shown, significance determined by Log-rank test

Back to article page