Nf1 Loss Promotes Kras-Driven Lung Adenocarcinoma and Results in Psat1-Mediated Glutamate Dependence (2019)
Figure 6

Figure 6. Nf1/NF1-Mutant Xenografts are Sensitive to Glutaminase and Aminotransferase Inhibition in Vivo

(A) Schematic describing KP and KPΔNF1 cell transplants into immunocompromised mice.

(B, C) Relative responses of subcutaneous KP and KPΔNF1 tumors treated with vehicle, (B) CB-839, or (C) AOA starting from day 12 and measured until day 27 (n = 6 tumors per cell line per treatment) and (D) the final masses of these tumors. Relative response = average tumor volume with treatment / average tumor volume with vehicle. Full experimental data provided in Appendix Fig. S7A-B.

(E, F) Relative responses of orthotopic KP and KPΔNF1 tumors treated with vehicle, (E) CB-839, or (F) AOA starting from day 12 and measured until day 27 (n = 24 mice per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle. Quantification of tumor growth by photon flux luminescence after orthotopic transplantation with KP or KPΔNF1 cells transduced with a luciferase vector. Full experimental data provided in Appendix Fig. S7C-D.

(G, H) Relative responses of subcutaneous KP-ix tumors harboring doxycycline (DOX)-inducible gain-of-function (GOF)-Fak1 cDNA treated with vehicle, (G) CB-839, or (H) AOA with or without DOX/PIP2 (n = 36 mice per treatment group). Relative response = average tumor volume with treatment / average tumor volume with vehicle. Full experimental data provided in Appendix Fig. S7E-F.

(I, J) Relative responses of subcutaneous patient-derived NF1-mutant (PDKN1 and PDKN2) and NF1-WT (PDK) LUAD tumors treated with vehicle, (I) CB-839, or (J) AOA starting from day 12 and measured until day 30 (n = 6 tumors per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle. Full experimental data provided in Appendix Fig. S7G-I.

(K, L) Relative responses of orthotopic patient-derived NF1-mutant (PDKN1 and PDKN2) and NF1-WT (PDK) LUAD tumors treated with vehicle, (K) CB-839, or (L) AOA starting from day 12 and measured until day 27 (n = 12 mice per cell line per treatment). Relative response = average tumor volume with treatment / average tumor volume with vehicle. Quantification of tumor growth by photon flux luminescence after orthotopic transplantation with KP or KPΔNF1 cells transduced with a luciferase vector. Full experimental data provided in Appendix Fig. S7J-L.

P-values are reported in Appendix Table S3. For bar charts, data presented as means with error bars representing standard deviations (SDs). For boxplots, whiskers indicate the minimum and maximum values, the upper and lower perimeters represent the first and third quartiles, the midline represents the median value, and the x symbol represents the mean.

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