Effects of nonselective cyclooxygenase inhibition with low-dose ibuprofen on tumor growth, angiogenesis, metastasis, and survival in a mouse model of colorectal cancer
ABSTRACT To determine whether the nonselective and relatively inexpensive nonsteroidal anti-inflammatory drug ibuprofen would be effective in inhibiting colorectal cancer and might improve mortality in a mouse model.
The effects of ibuprofen on tumor growth inhibition and animal survival have been examined in both mouse and human colorectal cancer tumor models. Angiogenesis was measured by in vitro endothelial cell tube formation and immunohistochemistry.
Ibuprofen significantly inhibited cell proliferation in mouse (MC-26) and human (HT-29) colorectal cancer cell lines. In vitro angiogenesis assays also indicated that ibuprofen decreased both cell proliferation and tube formation. The administration of chow containing 1,360 ppm ibuprofen, which achieved an average plasma concentration of ibuprofen lower than the peak level achieved in humans at therapeutic doses, inhibited tumor growth by 40% to 82%. Fewer liver metastases were found in the ibuprofen group compared with the control group. In combination therapy with the standard antineoplastic agents, 5-fluorouracil, or irinotecan (CPT-11), tumor volumes in the groups with ibuprofen +/- CPT-11 or 5-fluorouracil were smaller than in the control group. Ibuprofen was similar to the cyclooxygenase-2 selective inhibitor rofecoxib in its ability to suppress tumor growth and improve overall survival.
Ibuprofen, in part by modulating tumor angiogenesis, decreases both tumor growth and metastatic potential in mice. The ibuprofen doses were in the low range of therapeutic human plasma concentrations. Ibuprofen potentiates the antitumor properties of CPT-11 and improves survival of mice without increasing gastrointestinal toxicity.
SourceAvailable from: Kenneth J.D. Mackenzie[Show abstract] [Hide abstract]
ABSTRACT: A novel in situ synthesis is presented of a hydroxyapatite composite with the mesoporous silicate MCM-48 with potential applications as a drug delivery agent The structure and properties of this nanocomposite, investigated by a number of techniques including XRD, SEM and TEM, show the intergrowth of the hydroxyapatite particles with the silica structure. The bioactivity of the new material was determined by measuring the decrease in the calcium ion concentration of simulated body fluid (SBF) after soaking the nanocomposite, while the uptake of ibuprofen on MCM-48 and MCM-48/HAp composite from ethanol was monitored by UV spectroscopy at 222 nm which was also used to monitor the release of ibuprofen into SBF, MTT assay was used to assess effect of the sample on MG68 cell live proliferation. The results confirm the successful synthesis of a MCM-48/hydroxyapatite nanocomposite and its potential biomedical applications as a bioactive ceramic and as a drug delivery agent with a higher rate of ibuprofen release compared to MCM-48.Ceramics International 06/2014; 40(5):7355-7362. DOI:10.1016/j.ceramint.2013.12.079 · 2.09 Impact Factor
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ABSTRACT: Nanofibre forming peptide amphiphiles were conjugated to naproxen through an esterase-sensitive linker. The amount of naproxen released, in the presence of enzymes, was influenced by the linker conjugating the drug to the supramolecular assembly. In vitro studies showed the anti-inflammatory activity of the released drug was maintained.Chemical Communications 09/2014; 50(89). DOI:10.1039/c4cc06340f · 6.72 Impact Factor
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ABSTRACT: Numerous epidemiological studies have suggested effectiveness of long-term and regular use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and aspirin, in preventing and treatment of certain cancers including prostate, colon, breast, lung, and gastric cancers. We have studied the potential anti-turmeric effect of ibuprofen in adenocarcinoma gastric cell line (AGS). The effects of ibuprofen were investigated on cell proliferation, apoptosis, angiogenesis, and expression of stemness marker genes using real-time RT-PCR, DNA laddering, and tube formation assays via ECM gel and human umbilical vein endothelial cells (HUVECs). Annexin-V-FLUOS and propidium iodide (PI) were used to stain the apoptotic cells. Our findings indicate that ibuprofen at the concentrations of 100, 200, 300, 400, and 500 μM is able to reduce the cancerous characteristics of the AGS cells by inducing apoptosis, inhibition of cell proliferation, and angiogenesis. Real-time RT-PCR showed that ibuprofen altered the expression of several genes including Akt, P53, PCNA, Bax, and Bcl2 in the AGS cells. In addition, reduction in CD44 and OCT3/4 transcript levels revealed that ibuprofen reduces the stemness of the AGS cells and therefore it could be used as a potential anti-tumor drug.Tumor Biology 12/2014; DOI:10.1007/s13277-014-2952-3 · 2.84 Impact Factor