Figure 8.

Targeting ARHGEF12 with Y16 synergizes with docetaxel to suppress ovarian metastasis. (A) Cell viability analysis. AGS cells with sgARHGEF12 or sgCtrl were treated with docetaxel for 48 h. (B) Cell viability analysis. AGS cells with or without ectopic expression of ARHGEF12 (AGS/ARHGEF12) were treated with docetaxel for 48 h. (C-D) Synergistic effect analysis. AGS/EV (C) or AGS/ARHGEF12 (D) cells were treated with docetaxel (0.5 to 10 nM) or Y16 (5 to 40 µM), either alone or in combination for 48 h. Viability in the treatment groups was normalized to DMSO control. Analysis of the synergistic effect in docetaxel and Y16 combination was performed by SynergyFinder using zero interaction potency (ZIP) model. The box indicates the synergistic area. (E) Treatment schedules for the administration of docetaxel (5 mg/kg, intraperitoneal injection once daily), or/and Y16 (20 mg/kg, intraperitoneal injection once daily) to animals grafted with AGS/EV or AGS/ARHGEF12 cells (n = 6). Control animals received a placebo (vehicle). (F) Representative bioluminescence images in (E) on day 28. (G) Quantification of bioluminescence activity in panel (F). (H-I) Representative hematoxylin and eosin (H&E) staining images of the animal livers (H) and ovaries (I) with sensitive and resistant treatment. Scale bar, 100 µm and 20 µm. (J) Detailed summary of the peritoneal metastasis of animals after treatment. Data are representative of three independent experiments with similar results. Data were presented as mean ± SEM. n.s., no significant, ***P < 0.001, by two-tailed Student's t-test.