Octreotide induces caspase activation and apoptosis in human hepatoma HepG2 cells

作     者：Nikos J Tsagarakis Ioannis Drygiannakis Antonis G Batistakis George Kolios Elias A Kouroumalis 

作者机构：Liver Research LaboratorySchool of MedicineUniversity of Crete Laboratory of PharmacologySchool of MedicineDemocritus University of Thrace Department of Gastroenterology and HepatologyUniversity Hospital of Heraklion 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2011年第17卷第3期

页      面：313-321页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by Research funds of the Liver Research Laboratory School of Medicine University of Crete Greece 

主　　题：Octreotide Hepatocellular carcinoma Apoptosis Caspases Somatostatin 

摘      要：AIM: To investigate the role of octreotide on cellular proliferation and apoptosis of human hepatoma (HepG2) cells. METHODS: We studied cellular proliferation, apoptosis and the possible internal caspase-mediated apoptosis pathway involved, after treatment of HepG2 carcinoma cells with octreotide in comparison with the apoptosis caused by tumor necrosis factor-α (TNF-α). Activities of caspase-3, caspase-9, caspase-8 and caspase-2 were studied, while apoptosis was investigated through detection of DNA fragmentation and through identification of apoptotic cells with the annexin-V/propidium iodide flow cytometric method. RESULTS: After an initial increase in HepG2 cellular proliferation, a significant inhibition was observed with 10-8 mol/L octreotide, while TNF-α dose-dependently decreased proliferation. Early and late apoptosis was significantly increased with both substances. Octreotide significantly increased caspase-3, caspase-8 and caspase-2 activity. TNF-α signifi cantly increased only caspase-2. Cellular proliferation was decreased after treatment with octreotide or TNF-α alone but, in contrast to TNF-α, octreotide decreased proliferation only at concentrations of 10-8 mol/L, while lower concentrations increased proliferation. CONCLUSION: Our findings are suggestive of caspasemediated signaling pathways of octreotide antitumor activity in HepG2 cells, and indicate that measurements of serum octreotide levels may be important, at least in clinical trials, to verify optimal therapeutic drug concentrations.