Open AccessInhibition of early preneoplastic events in the rat liver by the somatostatin analog lanreotide
Author(s) -
Borbath Ivan,
Leclercq Isabelle A.,
AbarcaQuis Jorge,
Desaeger Christine,
Lebrun Valérie,
Moulin Pierre,
Sempoux Christine,
Horsmans Yves
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00626.x
Subject(s) - lanreotide , somatostatin , medicine , carcinogen , cyclin d1 , hepatocellular carcinoma , cancer research , endocrinology , apoptosis , cancer , cell cycle , biology , acromegaly , biochemistry , growth hormone , hormone
Hepatocellular carcinoma (HCC) is the third most common cause of cancer‐related death, and its incidence is increasing worldwide. Due to the known risk factors (mainly hepatitis B and C viruses), we believe there is a rationale for a chemopreventive approach to treat HCC. Here, based on described in vitro data, we evaluated the preventive effects of lanreotide, a somatostatin analog, on the induction of early carcinogenic events. We monitored preneoplastic foci induced by a two‐stage initiation/promotion model of hepatocarcinogenesis in male Wistar rats, using diethylnitrosamine and 2‐acetylaminofluorene. Lanreotide was given starting the day after the first diethylnitrosamine injection. By quantitative morphometry, we showed that lanreotide significantly decreases the size of induced preneoplastic foci. Analysis of proliferation and apoptosis assessed by immunohistochemistry, showed decreased proliferation and increased cell death in rats treated with lanreotide. As these events were associated with a significant decreased expression of the cell cycle regulator cyclin D1 and an increased expression of the cyclin‐dependent kinase inhibitor p27 kip1 compared to the non‐treated group, it is tempting to speculate that these factors are involved in the favorable effect of lanreotide. In conclusion, lanreotide significantly decreases early carcinogenic transformation in a two‐step rat model. As lanreotide has a low toxicity profile, we believe it would be interesting to evaluate its effect in chemoprevention of HCC. ( Cancer Sci 2007; 98: 1831–1839)