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. Author manuscript; available in PMC: 2021 Dec 1.
Published in final edited form as: Cancer Res. 2021 Mar 16;81(11):3051–3066. doi: 10.1158/0008-5472.CAN-20-2435

Fig. 7.

Fig. 7.

In vitro and in vivo sensitivity of osimertinib and rociletinib resistant cells to dactolisib, a PI3K/mTOR inhibitor, and in vitro sensitivity of osimertinib resistant cells to VX-970, an ATR inhibitor. (A) Cell viability curves of H1975, H1975-AZR 3 and 4 cells showing the effect of osimertinib, dactolisib, and dactolisib in presence of 2 μM of osimertinib treatment. The EC50 values and fold resistant of the AZR3 and AZR4 cells compared to H1975 sensitive cells are shown. (B) Cell viability curves of H1975, H1975-COR 1 and 10 cells showing the effect of rociletinib, dactolisib, and dactolisib in presence of 2 μM of rociletinib treatment. The EC50 values and fold resistance of COR1 and COR10 cells compared to H1975 sensitive cells are shown. (C-D) Cell viability curves of PC9, PC9-OsiR-NCI1 (C) and HCC827, HCC827-OsiR-NCI1 (D) cell lines showing the effect of osimertinib, dactolisib, and dactolisib in presence of 2 μM of osimertinib treatment. The corresponding EC50 of each drug is shown in the right panels. (E) Cell viability curves of H1975, H1975-AZR 3 and 4 cell lines showing the effect of VX-970, and VX-970 in presence of 2 μM of osimertinib treatment. The EC50 of VX970 alone or in presence of 2μM osimertinib are shown in the right panel. (F) Western blots showing changes in phosphorylation and total protein expression without TKI treatment and upon 1 hour of dactosilib (50nM), osimertinib (50nM) or a combination of dactolisib (50nM) and osimertinib (50nM) treatment in H1975, H1975-AZR3, and H1975-AZR4 cells (G) Western blots showing changes in phosphorylation and total protein expression without TKI treatment and upon 1 hour of dactosilib (50nM) or osimertinib (50nM) or a combination of dactolisib (50nM) and osimertinib (50nM) treatment treatment in PC9, PC9-OsiR-NCI1, HCC827, and HCC827-OsiR-NCI1 cells. (H-J) Dactolisib in combination with osimertinib inhibits tumor growth of H1975-AZR3 xenografts in vivo. The in vivo growth of xenograft tumors is shown for 20 days of treatment (H) and the percent tumor growth at Day 20 (I) and Day 36 (J) of treatment is shown.