The role and mechanisms of cyclooxygenase-2 inhibitors on the proliferation of hepatic stellate cell.
- Author:
Ya-jun HE
1
;
Jie PAN
;
Jian-chang SHU
;
Yan SHEN
;
Xia LV
;
Li FANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apoptosis; drug effects; Cell Cycle; drug effects; Cell Line; Cell Proliferation; drug effects; Cyclooxygenase 2; metabolism; Cyclooxygenase Inhibitors; administration & dosage; pharmacology; Dose-Response Relationship, Drug; Flow Cytometry; Hepatic Stellate Cells; drug effects; metabolism; Liver Cirrhosis; pathology; prevention & control; Nitrobenzenes; pharmacology; Proliferating Cell Nuclear Antigen; metabolism; Rats; Sulfonamides; pharmacology
- From: Chinese Journal of Hepatology 2009;17(5):346-349
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVESTo observe the effects of NS-398 on proliferation of hepatic stellate cells (HSCs) in vitro, and to investigate the possible molecule mechanism.
METHODSHSCs were incubated with different concentrations of NS-398. The effects of NS-398 on cell proliferation was detected by MTT colormetric assay. The cell cycle of HSCs was analyzed by Flow Cytometry (FCM), cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) proteins in HSCs were detected by immunocytochemistry.
RESULTSAdministration of 20-160 micromol/L NS-398 significantly inhibited HSCs proliferation in dose-dependent manner compared with the control group (P less than 0.01). After treated with NS-398 at concentrations of 90, 120, and 150 micromol/L for 48 h, the number of HSCs in G(2)/M phase increased and the number of HSCs in G(0)/G(1) phase decreased (P less than 0.05); Incubated with 120 micromol/L NS-398 for 48 h, percentage of masculine cell of PCNA was 28.91%+/-0.11%, which was significantly lower than that of the control group (85.99%+/-0.13%) (P less than 0.01). Percentage of masculine cell of COX-2 was 13.80%+/-0.43%, which was not significantly different from that of the control group (14.07%+/-0.59%) (P more than 0.05).
CONCLUSIONSNS-398 could inhibit the proliferation of HSC-T6 and arrest HSCs in G2/M phase. Down-regulation of PCNA protein may partially accounted for the proliferation inhibition effect on HSCs induced by NS-398.
