Synergistic Effect of Celecoxib on 5-fluorouracil-induced Apoptosis in Hepatocellular Carcinoma Patients
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 of...
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| Format: | Article |
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Elsevier
2010-10-01
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| Series: | Annals of Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268119316175 |
| _version_ | 1818607755587485696 |
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| author | Ahmad R. Bassiouny Amira Zaky Hashem M. Neenaa |
| author_facet | Ahmad R. Bassiouny Amira Zaky Hashem M. Neenaa |
| author_sort | Ahmad R. Bassiouny |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T14:31:48Z |
| format | Article |
| id | doaj.art-932735ee7882409d8529b9501ec0a31a |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-12-16T14:31:48Z |
| publishDate | 2010-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-932735ee7882409d8529b9501ec0a31a2022-12-21T22:28:13ZengElsevierAnnals of Hepatology1665-26812010-10-0194410418Synergistic Effect of Celecoxib on 5-fluorouracil-induced Apoptosis in Hepatocellular Carcinoma PatientsAhmad R. Bassiouny0Amira Zaky1Hashem M. Neenaa2Department of Biochemistry, Faculty of Science, Alexandria University, Egypt; Correspondence and reprint request:Department of Biochemistry, Faculty of Science, Alexandria University, EgyptDepartment of Internal Medicine, Faculty of Medicine, Alexandria University, EgyptBackground. 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.http://www.sciencedirect.com/science/article/pii/S1665268119316175HepatocarcinomaCelecoxib5-flourouracilApoptosis |
| spellingShingle | Ahmad R. Bassiouny Amira Zaky Hashem M. Neenaa Synergistic Effect of Celecoxib on 5-fluorouracil-induced Apoptosis in Hepatocellular Carcinoma Patients Annals of Hepatology Hepatocarcinoma Celecoxib 5-flourouracil Apoptosis |
| title | Synergistic Effect of Celecoxib on 5-fluorouracil-induced Apoptosis in Hepatocellular Carcinoma Patients |
| title_full | Synergistic Effect of Celecoxib on 5-fluorouracil-induced Apoptosis in Hepatocellular Carcinoma Patients |
| title_fullStr | Synergistic Effect of Celecoxib on 5-fluorouracil-induced Apoptosis in Hepatocellular Carcinoma Patients |
| title_full_unstemmed | Synergistic Effect of Celecoxib on 5-fluorouracil-induced Apoptosis in Hepatocellular Carcinoma Patients |
| title_short | Synergistic Effect of Celecoxib on 5-fluorouracil-induced Apoptosis in Hepatocellular Carcinoma Patients |
| title_sort | synergistic effect of celecoxib on 5 fluorouracil induced apoptosis in hepatocellular carcinoma patients |
| topic | Hepatocarcinoma Celecoxib 5-flourouracil Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S1665268119316175 |
| work_keys_str_mv | AT ahmadrbassiouny synergisticeffectofcelecoxibon5fluorouracilinducedapoptosisinhepatocellularcarcinomapatients AT amirazaky synergisticeffectofcelecoxibon5fluorouracilinducedapoptosisinhepatocellularcarcinomapatients AT hashemmneenaa synergisticeffectofcelecoxibon5fluorouracilinducedapoptosisinhepatocellularcarcinomapatients |