LSL-Kras(G12D) (B6N.Cg-Krastm4Tyj/CjDswJ) mice on a C57BL/6J background were purchased from The Jackson Laboratory. C57BL/6J mice were purchased from National Rodent Laboratory Animal Resources. The LSL-Kras(G12D) lung cancer mouse model was generated as previously described by our laboratory (25). Initially, 7-week-old LSL-Kras(G12D) mice were anesthetized with isoflurane via a gas chamber and infected with 5 × 107 infectious particles of Ad-Cre (HanBio) per mouse by intranasal injection. Mice were randomly divided into 4 groups 12 weeks after the operation. Mice were treated with vehicle, OTX015, and/or FX1 daily for 3 weeks. Next, mice were allowed to recover in the untreated condition for an additional week. On day 28, tumors were measured by micro-CT (PerkinElmer) after the final dosing. Meanwhile, 3 mice in each group were randomly sacrificed. Lung tissue was separated for H&E staining and immunohistochemical analysis. The remaining mice (n = 6 mice per group) were supported under basic animal care, with no further drug intervention, until their death. Survival rates were calculated by the Kaplan-Meier method. Statistical significance was assessed using log-rank tests.

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