Antiproliferative and proapoptotic effects of somatostatin on activated hepatic stellate cells.
OBJECTIVE
To assess the effects of somatostatin on proliferation and apoptosis of activated rat hepatic stellate cells (HSCs).


METHODS
HSCs isolated from the livers of adult Sprague-Dawley rats (weighing 400-500 g) by in situ perfusion and purified by single-step density gradient centrifugation with Nycodenz, became activated after 10 days' cultivation. Then the apoptotic rate of HSCs treated with different doses of somatostatin for 72 h, was assayed by acridine orange/ethidium bromide fluorescent staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, transmission electron microscopy and flow cytometry, while the proliferation of HSCs was measured by MTT assay. Furthermore, the mechanisms of somatostatin were investigated by cytodynamic analysis.


RESULTS
Somatostatin at the concentration of 10(-6)-10(-9) mol/L could decrease the proliferative rate, and promote the apoptosis of activated rat HSCs in a dose-dependent way. Its action was most significant when the concentration reached 10(-6) mol/L or 10(-7) mol/L (P<0.05-0.01). An obvious cell-cycle arrest (G(0)/G(1) arrest) was the important way for somatostatin to exert its action.


CONCLUSIONS
Antiproliferative and proapoptotic effects of low-dose somatostatin on activated rat HSCs can be obtained. These findings reveal its potential antifibrotic action.
Pan
Qin
Q
Department of Gastroenterology, Shanghai Second Medical University, Xinhua Hospital, 1665 KongJiang Rd., Shanghai 200092, China. fangchunhua@online.sh.cn
Li
Ding-Guo
DG
Lu
Han-Ming
HM
Lu
Liang-Yong
LY
Wang
Yu-Qin
YQ
Xu
Qin-Fang
QF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology*
D013004:Somatostatin