Inhibitory effect of amiloride on the urokinase plasminogen activators in prostatic cancer.
The diuretic drug amiloride (AMLD), which competitively inhibits the catalytic activity of urokinase plasminogen activators (UPA), was used to study its effects on the proteolytic enzymes implicated in the invasiveness and metastases in a prostatic tumor model carrying two different sublines of adenocarcinoma of the prostate. Our data showed that UPA activity was significantly higher, both in the cytosol and pellet of R3327-AT3, a fast-growing highly metastatic and androgen-insensitive tumor, as compared to the G3327-G subline, a slow-growing nonmetastatic tumor of the prostate. The UPA activity in AT3 tumor dropped when the rats were treated with AMLD for 3 weeks. The UPA activity in the sera and tumor effusions from rats with AT3 tumor was significantly higher as compared to those with G subline tumor. The number of pulmonary metastatic foci was the same in untreated rats as compared to those treated with AMLD. The lymph node inspection after 3 weeks revealed no secondary tumor in the AMLD-treated group. The role of UPA in the metastases of prostate cancer is discussed.
Ray
P
P
Division of Urology, Cook County Hospital, Chicago, IL 60612, USA.
Bhatti
R
R
Gadarowski
J
J
Bell
N
N
Nasruddin
S
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000556:secondary; D008297:Male; D009374:Neoplasms, Experimental; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004232:Diuretics; D000584:Amiloride; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator