Effect of cytochrome CYP2C19 on the anti-myeloma activity of thalidomide in vitro / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of human liver microsome on anti-myeloma activity of thalidomide (TH) in vitro and identify the role of cytochrome CYP2C19 in it.</p><p><b>METHODS</b>Human multiple myeloma (MM) cell lines U266, NCI-H929, RPMI 8226, LP-1 and CZ-1 were treated with TH or TH pre-incubated with human liver microsome. Cell viability was detected by MTT assay, and cell cycle and apoptosis by flow cytometry (FCM).</p><p><b>RESULTS</b>TH treatment had no direct effect on cell viability at concentrations of 10 microg/ml, 50 microg/ml and 100 microg/ml, the viabilities of the 5 MM cell lines were 96.2% - 103.7%, 96.3% - 103.7% and 97.9% - 106.5% respectively, being no significant difference from that of control (P > 0.05). However, when preincubated with human liver microsome, TH significantly inhibited the cell viability with a dose-dependent manner. At concentrations of 10 microg/ml, 50 microg/ml and 100 microg/ml, TH pre-incubated with human liver microsome led to 12.2% - 22.9%, 25.9% - 36.4% and 34.9% - 46.3% decreases of cell viability, respectively (P < 0.05). TH at concentration of 100 microg/ml pre-incubated with human liver microsome caused an increase of 18.5% - 32.5% in apoptosis cells. When omeprazole, a specific inhibitor of cytochrome CYP2C19, was added in the incubation system, the inhibition of cell viability by TH was weakened. At concentrations of 5 micromol/L and 10 micromol/L, omeprazole reversed the cell viability by 7.5% - 21.9% and 19.1% - 38.3%, respectively (P < 0.05).</p><p><b>CONCLUSION</b>Treatment of TH with human liver microsome is essential for its anti-myeloma activity in vitro, and cytochrome CYP2C19 is involved with this metabolism process.</p>