Figure 3

HQBA inhibits growth of mammary cancer in MMTV-Wnt1 and MMTV-PyMT mice. (a) Upper panel: female virgin MMTV-Wnt1 mice with palpable tumors were treated with 9 mg/kg per day HQBA (N=9). Seven of the nine mice showed initial regression of tumor volume for ∼2 weeks. Three of the nine mice showed steady regression throughout the 5-week study with final tumor volumes ∼20% of starting volume. Center panel: growth of tumors in control, vehicle-treated MMTV-Wnt1 mice. The tumor volume doubled on average every 5 days. Lower panel: mice were weighed daily as an indicator of drug toxicity. Both control and treated mice gained weight at the same rate throughout the study. (b) Representative images of hematoxylin- and eosin-stained small and large intestine from mice treated for 2 weeks with vehicle or 9 mg/kg per day of HQBA. No deterioration of crypt/villi structure was seen in any part of the intestine. (c) Female virgin MMTV-Wnt1 mice with palpable tumors were treated with 200 μl of 25 μM HQBA daily for up to 13 days. Differences in mouse body weight translated this dosage into a range of 60 to 90 mg/kg per day. Upper panel: average tumor volume in the treated group (N=5) regressed to 60% of starting volume by day 6 and returned to starting volume by the end of the study. By contrast, average tumor volume in the control group (N=3) increased almost 20-fold. Lower panel: mouse body weight did not vary between arms by >10% throughout the course of the study. (d) Tumor bearing virgin female MMTV-PyMT mice were treated for 14 days with vehicle (N=4), 20 mg/kg per day HQBA (N=5), or 70 mg/kg per day HQBA (N=2). HQBA markedly reduced tumor growth rate (upper panel) without an effect on weight gain (lower panel).