Research Paper Volume 12, Issue 13 pp 13220—13233

Cancer-associated fibroblasts-derived gamma-glutamyltransferase 5 promotes tumor growth and drug resistance in lung adenocarcinoma

Figure 6. Targeting GGT5 inhibits tumor growth and enhances the drug sensitivity of LUAD cells in vivo. (A) Inhibiting GGT5 activity with a small-molecule inhibitor GGsTop (i.p. injection, 1 mg/kg) suppresses the tumor growth in nude mice xenograft model. (B) IHC staining with antibody against Ki67 (a marker of proliferative cell) in tissue sections from transplantation tumors treated with DMSO control or GGsTop. (C) Co-administration of Cisplatin (i.p. injection, 6 mg/kg) and GGsTop (i.p. injection, 1 mg/kg) significantly inhibits the tumor growth. (D) Schematic diagram for high level of GGT5 in CAFs contributing to LUAD cell survival and drug resistance by increasing intracellular GSH and decreasing the intracellular ROS level in tumor cells. In panels A and C, data represent mean ± SD, and in panel B, data represent mean ± SEM. In panels A-C, *, P < 0.05; **, P < 0.01; ***, P < 0.001.