Effect of erythropoietin, 5-fluorouracil and SN-38 on the growth of DLD-1 cells.
Journal Title: Pharmacological Reports - Year 2010, Vol 62, Issue 5
Abstract
Supplementation of recombinant human erythropoietin (rHuEpo) is one of the methods for the treatment of anemia. The influence of rHuEpo on proliferation or clonogenic growth of cancer cells is not clear and some of the published results are conflicting. The aim of this work was to study the effect of rHuEpo on colon cancer cells when given alone or in combination with cytostatics. Human colon adenocarcinoma cells (DLD-1) were cultured in medium with rHuEpo, 5-fluorouracil (5-FU) and an active metabolite of irinotecan (SN-38). Cell viability was determined using a hematocytometer and 0.4% (w/v) trypan blue dye. Cell proliferation was measured by the MTT assay. Expression of EpoR, Bax, Bcl-2 and Akt1 protein was assessed by Western blot. The results of this study indicate a dose-dependent inhibitory effect of rHuEpo on DLD-1 cell growth and proliferation. Moreover, the combined treatment of rHuEpo and cytotoxic agents such as 5-FU and SN-38 increases the antitumor action, which is indicated by decreases in proliferation in the MTT test, cell numbers and DNA synthesis. We found a significant increase in EpoR, Bcl-2 and Akt1 protein expression in all cells grown in medium containing 3 IU of rHuEpo. We observed that EpoR is constitutively expressed in DLD-1 cells. Our results indicate that rHuEpo acts via EpoR to directly inhibit DLD-1 cell growth and indirectly modulate the cytostatics effects of 5-FU and SN-38.
Authors and Affiliations
Anna Tankiewicz-Kwedlo, Dariusz Pawlak, Tomasz Domaniewski, Włodzimierz Buczko
Keywords
Related Articles
- EP ID EP129331
- DOI -
- Views 95
- Downloads 0
Administration of L-carnitine and mildronate improves endothelial function and decreases mortality in hypertensive Dahl rats.
Hypertension is a well established risk factor for the development of cardiovascular diseases and increased mortality. This study was performed to investigate the effects of the administration of L-carnitine or mildronat...
Molecular determinants of heart failure with normal left ventricular ejection fraction.
In population-based studies, heart failure with normal left ventricular (LV) ejection fraction (HFNEF) is now increasingly recognized and referred to as diastolic heart failure. However, the pathogenic mechanisms underly...
Potential pitfalls of propofol target controlled infusion delivery related to its pharmacokinetics and pharmacodynamics.
Target controlled infusion (TCI) devices are increasingly used in clinical practice. These devices unquestionably aid optimization of drug dosage. However, it still remains to be determined if they sufficiently address d...
Cytochrome P450-dependent metabolism of omega-6 and omega-3 long-chain polyunsaturated fatty acids.
Dietary fish oil omega-3 fatty acids (n-3 PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against arrhythmia and sudden cardiac death using largely unknown mechanisms. EPA and DHA may...
Short review on dopamine agonists: insight into clinical and research studies relevant to Parkinson's disease.
Parkinson's disease (PD) is a chronic and progressive neurological disorder characterized by selective degeneration of dopaminergic neurons (DAergic) in the substantia nigra pars compacta (SNpc) and subsequent decrease i...