BACKGROUND: MMPs have been implicated in the process of metastasis. Matlystatin analogue, called R-94138, isolated from Actinomadura atramentaria, has been reported to inhibit the activity of MMP-2 and -9 specifically. In this study, we investigated the effect of R-94138 on the invasive and lymphnodal metastatic ability of gastric cancer cells. MATERIALS AND METHODS: Three gastric cancer cell lines, MKN-28, MKN-45, MKN-74, and two colorectal cancer cell lines, HT-29, and LS174T were used. The invasion ability of these cell lines were assayed with R-94138 at the required concentration in vitro. The In vivo effect of R-94138 on lymphnode metastasis was examined passaged by orthotopic implantation. RESULTS: All cell lines revealed activity of both 72 and 92 kDa forms of MMPs by gelatin zymography. R-94138 significantly inhibited the invasiveness of all of these cells to the extracellular matrix. The number of lymph node metastases and the amount of body weight loss were significantly decreased by intraperitoneal administration of R-94138. CONCLUSION: MMP inhibitor, R-94138, has a possible application in adjunctive therapy for lymph node metastasis in gastric carcinoma.
BACKGROUND: MMPs have been implicated in the process of metastasis. Matlystatin analogue, called R-94138, isolated from Actinomadura atramentaria, has been reported to inhibit the activity of MMP-2 and -9 specifically. In this study, we investigated the effect of R-94138 on the invasive and lymphnodal metastatic ability of gastric cancer cells. MATERIALS AND METHODS: Three gastric cancer cell lines, MKN-28, MKN-45, MKN-74, and two colorectal cancer cell lines, HT-29, and LS174T were used. The invasion ability of these cell lines were assayed with R-94138 at the required concentration in vitro. The In vivo effect of R-94138 on lymphnode metastasis was examined passaged by orthotopic implantation. RESULTS: All cell lines revealed activity of both 72 and 92 kDa forms of MMPs by gelatin zymography. R-94138 significantly inhibited the invasiveness of all of these cells to the extracellular matrix. The number of lymph node metastases and the amount of body weight loss were significantly decreased by intraperitoneal administration of R-94138. CONCLUSION: MMP inhibitor, R-94138, has a possible application in adjunctive therapy for lymph node metastasis in gastric carcinoma.
Authors: Franziska Leipoldt; Javier Santos-Aberturas; Dennis P Stegmann; Felix Wolf; Andreas Kulik; Rodney Lacret; Désirée Popadić; Daniela Keinhörster; Norbert Kirchner; Paulina Bekiesch; Harald Gross; Andrew W Truman; Leonard Kaysser Journal: Nat Commun Date: 2017-12-06 Impact factor: 17.694