The effect of octreotide and bromocriptine on expression of a pro-apoptotic Bax protein in rat prolactinoma.
It is well established that disruption of apoptosis may lead to tumor initiation, progression or metastasis. It is also well documented that many anticancer drugs induce apoptosis. In the earlier studies, the dopamine D2 receptor agonist bromocriptine (BC) and somatostatin analog octreotide (OCT) were found to inhibit the growth of the estrogen-induced rat prolactinoma. Our previous investigations, applying the TUNEL method showed the involvement of the pro-apoptotic effect in the action of BC, and to a lesser degree, in the action of OCT. The aim of the present study was to investigate whether the pro-apoptotic action of these drugs involves the increased expression of Bax--a member of Bcl-2 protein family which is known to play an important role in the regulation of apoptosis. Male four-week Fisher 344 rats were used in the experiment. Capsules containing diethylstilboestrol (DES) were implanted subcutaneously. Six weeks after the implantation the rats were given OCT (2 x 25 microg/animal/24), BC (3 mg/kg b.w./24 h) or OCT and BC at the above doses for 10 days. Bax expression was detected by immunohistochemistry. Prolactin (PRL) in blood serum was measured by radioimmunoassay (RIA). It has been found that both OCT and BC, alone or in combination, significantly reduce the tumor weight. Both OCT and BC suppressed PRL levels, but the inhibitory effect of BC was stronger than that of OCT. It has been found that the treatment with OCT and BC, alone or in combination, causes a significant increase in Bax expression in the rat prolactinoma cells. Our findings indicate that anti-tumoral action of bromocriptine and to some extent the action of octreotide in the experimental rat prolactinoma is connected with the induction of apoptosis and is associated with increased Bax expression.
Gruszka
Anna
A
Department of Experimental Endocrinology and Hormone Diagnostics, Institute of Endocrinology, Medical University, Lódź, Poland. agruszka@mp.pl
Kunert-Radek
Jolanta
J
Pawlikowski
Marek
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001971:Bromocriptine / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000096:biosynthesis / Q000235:genetics; D015175:Prolactinoma / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D011916:Rats, Inbred F344; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D006727:Hormone Antagonists; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D001971:Bromocriptine; D011388:Prolactin; D015282:Octreotide