Objective: To investigate the anti-cancer effect of tissue inhibitor of metalloproteinase-3 (TIMP-3) and its mechanism of action.
Methods: Recombinant TIMP-3(rTIMP-3) was prepared and used to study its effect on tumor growth and metastases in mice, and its effect on angiogenesis in chicken embryo allantoic membrane (CAM).
Results: rTIMP-3 was able to inhibit growth of subcutaneously implanted S180 sarcoma and hepatic carcinoma H22 in a dose-dependent manner. When the rTIMP-3 was given i.p. at a daily dose of 20 mg/kg body weight for 10 days, the growth of S180 sarcoma and H22 carcinoma was inhibited by 63.2% and 73.4%, respectively. The metastases of i.v. injected Lewis lung carcinoma(3LLC) was also suppressed by rTIMP-3, with an inhibition rate of 59.8%. rTIMP-3 was found to significantly inhibit angiogenesis in CAM assay.
Conclusion: rTIMP-3 has anti-cancer activity, and the mechanism of action might be associated with its inhibition on extracellular matrix degradation and anti-angiogenesis.