Effects of pentosan polysulfate sodium on the estrogen-induced pituitary prolactinoma in Fischer 344 rats.
The development of estrogen-induced pituitary prolactinoma in Fischer 344 (F344) rats is associated with enhanced neovascularization. This type of tumor is a rich source of basic fibroblast growth factor (bFGF), which possesses strong mitogenic and angiogenic properties. Pentosan polysulfate sodium (PPS) has been shown to exert antitumor activity by antagonizing the binding of bFGF to cell surface receptors. We have examined the effects of pentosan on tumor growth, hyperprolactinemia and angiogenesis in diethylstilbestrol-induced anterior pituitary adenoma in F344 rats. Chronic treatment with PPS did not cause any changes in the pituitary weight and serum prolactin concentration in comparison with untreated animals. The density of microvessels identified by CD-31 was also not affected by the tested drug. On the other hand, pentosan has been found to decrease cell proliferation evaluated by a number of PCNA-positive stained cell nuclei. Moreover, the TUNEL method has revealed an increased number of apoptotic bodies within the anterior pituitary after treatment with PPS. Despite the antiproliferative and proapoptotic activity of pentosan, the drug failed to inhibit tumor growth. This fact might be due to the lack of antiangiogenic activity of PPS in this experimental design.
Mucha
Slawomir
S
Institute of Endocrinology, Medical University of Lodz, 91-425 Lodz, Poland. g.m-mucha@wp.pl
Melen-Mucha
Gabriela
G
Stepien
Tomasz
T
Godlewski
Andrzej
A
Stepien
Henryk
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004054:Diethylstilbestrol; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010426:Pentosan Sulfuric Polyester / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000098:blood supply / Q000139:chemically induced / Q000188:drug therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D015175:Prolactinoma / Q000098:blood supply / Q000139:chemically induced / Q000188:drug therapy*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D010426:Pentosan Sulfuric Polyester; D004054:Diethylstilbestrol; D011388:Prolactin