Effects of angiotensin Ⅱ receptor antagonist, Losartan on the apoptosis, proliferation and migration of the human pancreatic stellate cells

摘要

AIM: To investigate the effects of AT_1 (Type 1 angiotensin II receptor) antagonist (Losartan) on the apoptosis, proliferation and migration of the human pancreatic stellate cells (hPSCs). METHODS: hPSCs were isolated from pancreatic sample of patients with pancreatic carcinoma using radioimmunoassay (RIA) technique to detect the concentration of AngII in culture media and cell homogenate. Immunocytochemistry (ICC) and in situ hybridization (ISH) methods were utilized to test AT_1 expression in hPSCs. Effects of Losartan on hPSCs proliferation, apoptosis and migration were investigated using BrdU incorporation, TUNEL, flow cytometry (FCM), and phase-contrast microscope separately when cells treated with Losartan. Immunofluorescence and Western blot were applied to quantify the expression of type Ⅰ collagen in hPSCs. RESULTS: There exists AT_1 expression in hPSCs, while no AngII was detected in culture media and cell homogenate. Losartan induces cell apoptosis in a dose-and time-dependent manner (apparently at 10~(-5) mol/L), no pro-proliferative effect was observed in the same condition. Corresponding dosage of Losartan can also alleviate the motion capability and type I collagen content of hPSCs compared with AngII treatment and non-treatment control groups. CONCLUSION: These findings suggest that paracrine not autocrine functions of AngII may have effects on hPSCs, which was mediated by AT_1 expressed on cells, while Losartan may exert anti-fibrotic effects by inhibiting hPSCs motion and partly by inducing apoptosis.