The Study Of The Celecoxib Mechanism In Vitro Action

Background: Celecoxib, as a kind of non-steroidal anti-inflammatory drugs listedsince1999, has been used as a clinical treatment for osteoarthritis, rheumatoidarthritis. Early epidemiological investigation, clinical trials and animalexperiments showed that the celecoxib can produce a wide variety of tumorprevention and cure effect, but also has synergistic effect with chemotherapysensitizing effect. Other than its clear effect in vivo, the studies of its mechanismin vitro has not been able to achieve a breakthrough, but the great concentrationdifferences between in vitro and in vivo studies can be a big inevitable question.Animal and clinical studies have found that the peak concentration of the bloodmedicinal concentration is only1-10μM, but the studies t in vitro often selected60-100μM as a target concentration to observed the changes in biologicalsignaling pathways. The dramatic difference between the concentration of vivoand vitro studies has become the biggest question for its mechanism research.Objective: By analyzing celecoxib‘s various special experiments, relatedinfluential factors and the discontinuing factors in vitro, we try to explore themechanism in vitro action.Materials and Methods: Determination of celecoxib-related factors in a varietyof tumor cell lines, normal cell lines, the role of the characteristics and the relatedinfluencing factors by MTT assay, The absorbance of staphylococcus aureus andhemoglobin was used to reflect the inhibitory effect and hemolysis of celecoxib,Combined with microscopic imaging of drug action and some physical effects ofcelecoxib in vitro, we try to explore the real mechanism in vitro action.Results:1. Celecoxib can inhibit the growth of tumor cell lines, normal cell linesand Staphylococcus aureus, this inhibition effect have the similar inhibition curves,when attain to a higher concentrations (post180μM), the drug will cause rapidlyhemolysis of erythrocytes;2.The vitro effect of the drug has a clear sectionconcentration characteristics, different intervals concentrations show significantlyrespective characteristics;3. The free-undissolved form of celecoxib in vitroculture medium play the major role in vitro action, those factors which can influence the free form of the drug can significantly change the drug action invitro, just as comprising serum levels, the medium protein content, thetemperature of the medium in the configuration process, ultrasonic disposal,different storage time after configure and so on;4.In vitro effect of the drug can besuspended in some conditions, while the hemolysis caused by higherconcentrations will appear again after recovery to the normal reaction conditions;5.Celecoxib has a special role to eliminate air bubbles in20%serum-containingmedium.Conclusion: The vitro effect of the drug is a non-specific physical mechanisms,Free-undissolved form of celecoxib in vitro culture medium play the major role invitro action, and different diameters particles can form in vitro with the changes ofthe drug concentration and the environment of the configuration. Differentdiameters particles may form different effects in vitro, Some of which may besuspended and continued under certain conditions.