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奥曲肽和溴隐亭对实验性大鼠催乳素瘤的抗肿瘤作用:抗增殖和促凋亡作用

Anti-tumoral action of octreotide and bromocriptine on the experimental rat prolactinoma: anti-proliferative and pro-apoptotic effects.

作者信息

Gruszka A, Pawlikowski M, Kunert-Radek J

机构信息

Department of Experimental Endocrinology and Hormone Diagnostics, Institute of Endocrinology, Medical University of Lodz, Sterling Str. 3, 91-425 Lodz, Poland.

出版信息

Neuro Endocrinol Lett. 2001 Oct;22(5):343-8.

PMID:11600876
Abstract

OBJECTIVES

The purpose of the study was to compare the effects of bromocriptine (BC) - D-2 receptor agonist and octreotide (OCT) - somatostatin analog on the tumor weight, prolactin (PRL) secretion, cell proliferation and apoptosis in the diethylstilboestrol (DES)-induced rat prolactinoma.

MATERIAL AND METHODS

Male four-week Fisher 344 rats were used in the experiment. The animals were implanted subcutaneously (s.c.) with capsules containing DES. Six weeks after the implantation the rats were given OCT (2 x 25 microg/animal/24 h s.c.) or BC (3 mg/kg b.w./24 h s.c.) for 10 days. The incorporation of bromodeoxyuridine (BrDU) into the tumor cell nuclei was used as an index of cell proliferation (labeling index - LI). The labeling of nuclear DNA fragmentation according to the TUNEL method was considered as an index of apoptosis (AI). PRL was measured by radioimmunoassay (RIA).

RESULTS

It has been found that OCT and BC significantly decreased the tumor weight and LI of tumor cells to the same extent. Both OCT and BC suppressed the PRL levels, but the inhibitory effect of BC was stronger than that of OCT. BC and OCT significantly enhanced the number of apoptotic cells in the tumor, but the pro-apoptotic effect of BC was more pronounced. The joint treatment exerted additive effects on tumor mass reduction, PRL secretion and cell proliferation, but OCT attenuated the pro-apoptotic effect of BC.

CONCLUSIONS

Summing up, both OCT and BC inhibit PRL secretion and cell proliferation. The anti-tumoral action of BC, and to some extent the action of OCT, is also connected with induction of apoptosis.

摘要

目的

本研究旨在比较溴隐亭(BC)——一种D-2受体激动剂和奥曲肽(OCT)——一种生长抑素类似物,对己烯雌酚(DES)诱导的大鼠催乳素瘤的肿瘤重量、催乳素(PRL)分泌、细胞增殖和凋亡的影响。

材料与方法

实验采用四周龄雄性Fisher 344大鼠。将含有DES的胶囊皮下植入动物体内。植入六周后,给大鼠皮下注射OCT(2×25微克/动物/24小时)或BC(3毫克/千克体重/24小时),持续10天。将溴脱氧尿苷(BrDU)掺入肿瘤细胞核作为细胞增殖指标(标记指数-LI)。根据TUNEL法标记核DNA片段化被视为凋亡指标(AI)。采用放射免疫分析法(RIA)测定PRL。

结果

发现OCT和BC均能显著降低肿瘤重量,并使肿瘤细胞的LI降低到相同程度。OCT和BC均能抑制PRL水平,但BC的抑制作用强于OCT。BC和OCT均能显著增加肿瘤中的凋亡细胞数量,但BC的促凋亡作用更明显。联合治疗在减轻肿瘤肿块、PRL分泌和细胞增殖方面发挥相加作用,但OCT减弱了BC的促凋亡作用。

结论

综上所述,OCT和BC均能抑制PRL分泌和细胞增殖。BC的抗肿瘤作用以及在一定程度上OCT的作用也与诱导凋亡有关。

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