TY - JOUR
T1 - Anti-metastatic and anti-angiogenic activities of a new matrix metalloproteinase inhibitor, TN-6b
AU - Lee, S. J.
AU - Sakurai, H.
AU - Oshima, K.
AU - Kim, S. H.
AU - Saiki, I.
N1 - Funding Information:
This study was supported, in part, by a Grant-in-Aid for Cancer Research (No. 14030028) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by a Grant-in Aid for Leading Regional Utilizing Potential of Regional Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2003/7
Y1 - 2003/7
N2 - We investigated the anti-metastatic and anti-angiogenic effects of TN-6b, a new broad-spectrum inhibitor of matrix metalloproteinases (MMPs), against Lewis lung carcinoma (LLC) and hepatic sinusoidal endothelial (HSE) cells. TN-6b potently inhibited the activities of MMP-2 and -9 secreted by LLC and HSE cells in a zymogram assay. TN-6b, at non-cytotoxic concentrations, caused a marked inhibition of invasion and migration of LLC, and tube-like formation of HSE cells. In contrast, TN-6d, an inactive enantiomer of TN-6b, did not inhibit the invasion and tube-like formation. Daily subcutaneous (s.c.) administration of TN-6b at doses of 30 and 60 mg/kg in mice resulted in a potent inhibition of tumour-induced angiogenesis of B16 melanomas and lymph node metastasis of LLC cells. In conclusion, TN-6b effectively inhibited lymph node metastasis of LLC cells through its anti-invasive and anti-angiogenic properties. These findings suggest that the MMP inhibition correlates well with its anti-angiogenic and anti-metastatic efficacy and TN-6b has the therapeutic potential to inhibit angiogenesis and metastasis in vivo and in vitro.
AB - We investigated the anti-metastatic and anti-angiogenic effects of TN-6b, a new broad-spectrum inhibitor of matrix metalloproteinases (MMPs), against Lewis lung carcinoma (LLC) and hepatic sinusoidal endothelial (HSE) cells. TN-6b potently inhibited the activities of MMP-2 and -9 secreted by LLC and HSE cells in a zymogram assay. TN-6b, at non-cytotoxic concentrations, caused a marked inhibition of invasion and migration of LLC, and tube-like formation of HSE cells. In contrast, TN-6d, an inactive enantiomer of TN-6b, did not inhibit the invasion and tube-like formation. Daily subcutaneous (s.c.) administration of TN-6b at doses of 30 and 60 mg/kg in mice resulted in a potent inhibition of tumour-induced angiogenesis of B16 melanomas and lymph node metastasis of LLC cells. In conclusion, TN-6b effectively inhibited lymph node metastasis of LLC cells through its anti-invasive and anti-angiogenic properties. These findings suggest that the MMP inhibition correlates well with its anti-angiogenic and anti-metastatic efficacy and TN-6b has the therapeutic potential to inhibit angiogenesis and metastasis in vivo and in vitro.
KW - Angiogenesis
KW - Lymph node metastasis
KW - MMP inhibitor
UR - http://www.scopus.com/inward/record.url?scp=0037632207&partnerID=8YFLogxK
U2 - 10.1016/S0959-8049(03)00375-7
DO - 10.1016/S0959-8049(03)00375-7
M3 - 学術論文
C2 - 12855272
AN - SCOPUS:0037632207
SN - 0959-8049
VL - 39
SP - 1632
EP - 1641
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 11
ER -
