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. Author manuscript; available in PMC: 2021 Sep 1.
Published in final edited form as: Mol Cancer Res. 2020 Nov 10;19(3):485–497. doi: 10.1158/1541-7786.MCR-20-0414

Figure 4. Combination of AXL and ATR inhibitors causes significant DNA damage and induces markers of mitotic catastrophe.

Figure 4.

A. Expression of key DDR and RS markers following treatment of TP53-deficient lung cancer cell lines Calu-1, H2250, H1299 and 344SQ with BGB324, VX-970 or their combination (1μM) for 24 h analyzed by western blotting. β-Actin was used as loading control. B. Immunoblots of Calu-1 and H1299 cells treated with BGB324, VX-970, or their combination for indicated durations. Hydroxyurea (0.5mM) was used as a positive control for RS. Changes in RS markers (pCHK1, pRPA32) and DNA damage (γH2Ax) seen as early as 4 h post treatment with BGB324/VX-970 combination. C. Similar increases in DNA damage and RS markers were observed in Calu-1 and H1299 cells treated with BGB324 and another ATR inhibitor, AZD6738. D. 344SQ shCTRL and 344SQ AXL knockdown cells were treated with 0.5μM VX-970 for 4 h or 24 h. Expression of DNA damage and RS markers were analyzed by western blotting. E. Increases in DNA damage and RS markers were not as pronounced in TP53-wildtype cell lines treated with BGB324/VX-970 combination.