Synergistic effect of Celecoxib on 5-fluorouracil-induced apoptosis in hepatocellular carcinoma patients

Autores: Bassiouny Ahmad R, Zaky Amira, Neenaa Hashem M

Resumen

Background: Cyclooxygenase-2 (COX-2) enzyme over expression is reported in many human HCC cell line studies and is linked to tumor cell resistance to chemotherapy-induced apoptosis. We hypothesized that adding a COX-2 inhibitor would improve the therapeutic benefits in patients with HCC. COX-2 is often increased and involved in drug resistance and poor prognosis. Method: Between January 2001 and December 2007, 15 patients with MDR-positive-HCC from 34 HCC patients based on tissue and serum liver of glypican-3 and fitting the preset eligibility criteria, were treated with a combination regimen with intravenous infusion of (5-FU) 750 mg once per week, 100mg/day cyclophosphamide (Endoxan) and 400 mg/day celecoxib taken orally in divided doses, while the rest of the patients received only 5-FU and Endoxan. Twenty-one patients (62%) had liver disease associated with hepatitis C virus (HCV) and 5 patients with hepatitis B virus (62%). Results: We found that celecoxib reduced P-glycoprotein with activation of caspase-3 and marked regression of tumor sizes. Sera angiogenic factors (VEGF & bFGF) levels measurement in HCC patients indicated that, the sera levels of both angiogenic factors were reduced significantly (p < 0.05) after treatment. Based on the tumor markers AFP & Glypican-3, 11 of the patients had a PR (11/15), including 3 patients who had normalization of AFP, and four patients had CR (4/15). Conclusions: These data suggest that the combination of 5-FU, Endoxan and Celecoxib is highly effective palliative regimen for patients with HCC with good performance status (score £ 3). The study suggests a framework for Celecoxib-based combination treatment of HCC.

Palabras clave: Hepatocarcinoma celecoxib 5-flourouracil apoptosis.

2010-10-27   |   923 visitas   |   Evalua este artículo 0 valoraciones

Vol. 9 Núm.4. Octubre-Diciembre 2010 Pags. 410-418 Ann Hepatol 2010; 9(4)