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. 2022 Sep 7;82(21):4044–4057. doi: 10.1158/0008-5472.CAN-21-4443

Figure 3.

Figure 3. The VRK1–VRK2 synthetic lethality is maintained in vivo. A, 14-day colony forming assays in U251MG VRK2-low cell line the absence or presence of 1 μg/mL doxycycline to induce VRK1 knockdown (left) and quantification (right) *, P < 0.05; **, P < 0.001, two-tailed t test. B, Assay similar to (A) in the U251MG VRK2-high cell line. C, Immunoblots from (A) to (B) at 1, 2, 5, and 7 days after doxycycline treatment. D, Immunoblots from U251MG VRK2-low and VRK2-high xenografts in tumor-bearing mice treated with or without 25-mg/kg doxycycline QD for 7 days . E, Tumor growth curves in mice bearing established 150 mm3 U251MG VRK2-low xenografts were treated with the indicated treatments. Data are presented as mean tumor volume ± SEM with 9 mice/data point up to day 42 ****, P < 0.0001 (two-tailed t test at day 42). F, 7-day and endpoint immunoblots tumors from (E). G, Tumor growth curves as in (E) with U251MG VRK2-high xenografts. Data are presented as mean tumor volume ± SEM with 9 mice/data point, *, P = 0.032 (two-tailed t test at day 24)

The VRK1–VRK2 synthetic lethality is maintained in vivo. A, Fourteen-day colony forming assays in U251MG VRK2-low cell line in the absence or presence of 1 μg/mL doxycycline to induce VRK1 knockdown (left) and quantification (right). *, P < 0.05; **, P < 0.001, two-tailed t test. B, Assay similar to A in the U251MG VRK2-high cell line. C, Immunoblots from A to B at 1, 2, 5, and 7 days after doxycycline treatment. D, Immunoblots from U251MG VRK2-low and VRK2-high xenografts in tumor-bearing mice treated with or without 25-mg/kg doxycycline QD for 7 days. E, Tumor growth curves in mice bearing established 150 mm3 U251MG VRK2-low xenografts were treated with the indicated treatments. Data are presented as mean tumor volume ± SEM with 9 mice/data point up to day 42. ****, P < 0.0001 (two-tailed t test at day 42). F, Seven-day and endpoint immunoblots tumors from E. G, Tumor growth curves as in E with U251MG VRK2-high xenografts. Data are presented as mean tumor volume ± SEM with 9 mice/data point. *, P = 0.032 (two-tailed t test at day 24). ns, not significant.