Figure 1.
The in vivo and in vitro antitumor activity of 194-A in the 4T1 orthotopic graft model. (a) and (b) Tumor growth inhibition after treatment with 194-A. 4T1-Luc+ (5 × 105 cells/mouse) were orthotopically implanted into the fat pad of male BALB/c mice. The tumor growth inhibition by p.o. administration of 194-A at different dosages (10~50 mg/kg/day) was monitored based on emitted bioluminescence detection (a) or external measurement using a caliper (b). (c) and (d) 194-A induced inhibition of proliferation and induction of apoptosis in 4T1 orthotopic grafts. Proliferation index and apoptotic index were determined by PCNA immunohistochemical staining (c) and TUNEL assay (d), respectively, after 10-day 194-A treatment. PCNA-positive or TUNEL-positive cells were counted in five 200x fields per 4T1 tumor section (n = 6). The average number of PCNA-positive or TUNEL-positive cells in each section was normalized to vehicle control. (e) 194-A (1~10 μM) have no significant effects on 4T1 cells proliferation as measured by MTS analysis. Lines or columns, mean (n = 6); bars, SE. *P < 0.05; **P < 0.01 as compared to the vehicle control group. Scale bar, 20 μm. (f) 194-A plasma concentration in mice after a single p.o. dose of 50 mg/kg (n = 3).