Inhibition of the growth of squamous cell carcinoma by tetrathiomolybdate-induced copper suppression in a murine model

Objective: To determine whether long-term therapy with tetrathiomolybdate suppresses tumor growth in an animal model. Design: In vivo murine model. Subjects: Thirteen 8-week-old C3H/HeJ mice, randomly assigned to a tetrathiomolybdate treatment group (n = 7) or a control group (n = 6). Interventions: To render the treatment group mice copper deficient, tetrathiomolybdate (0.7 mg/d per mouse) was added to their drinking water on days 1 through 20. Control group mice received only fresh drinking water. A flank injection of 1.5 X 10(5) SCCVII/SF cells was administrated to all mice on day 21. The treatment group mice continued to receive daily tetrathiomolybdate throughout the remainder of the experiment (70 days). Tumor volume measurements (square of the width X length X 0.52) were taken every other day beginning on day 40. Main Outcome Measures: Mean tumor volume differences. Results: Mean+/-SD tumor volumes on day 40 were 146+/-263 mm(3) (n=7) and 274+/-331 mul 3 (n=6) for the treatment and control groups, respectively. By day 54, the mean tumor volume for the treatment group was 65 0 mul 3, compared with 1716+/-960 mm(3) for the control group (P<.001). Treatment was withheld on day 54, resulting in a dramatic increase in tumor growth in the treatment group mice such that by day 60, there was no significant difference in mean tumor volume between groups. Conclusion: This study demonstrates the ability of tetra-thiomolybdate to maintain a significant and reversible suppression of long-term tumor growth in this murine model of squamous cell carcinoma, suggesting a potential application for the use of tetrathiomolybdate in human squamous cell carcinoma.