|
The effect of antitumor agents on the expression and activity of cytochrome P450 subfamily 2C
Uher, Tomáš ; Dračínská, Helena (advisor) ; Feglarová, Tereza (referee)
Targeted therapies, acting by blocking essential biochemical pathways required for tumor cell growth and survival, are being used lately in multiple cases of cancer treatment. Cabozantinib, a small molecule inhibitor of receptor tyrosine kinases, is an example of a targeted drug, regulating growth, angiogenesis and metastatic pro- gression of medullary thyroid cancer. Such drugs are also often complemented by cytotoxic agents, e.g. ellipticine; however, therapeutic usage of ellipticine itself is limited due to its poor solutibility and variety of adverse effects. In this bachelor thesis, effects of cabozantinib, ellipticine, or their combina- tion on gene and protein expression of cytochromes P450 2C6 and 2C11 have been studied in vivo. Aforementioned cytochromes have an important role in biotrans- formation of xenobiotics in rat liver. Their protein expression has been assessed by Western blot immunoassay technique, while the gene expression was evaluated by quantitative PCR method. Furthermore, the effects of studied substances and their combination on CYP2C6 and CYP2C11 specific activity have been determined by diclofenac 4'-hydroxylation and testosterone 16α-hydroxylation, respectively. Additionally, direct inhibitory effect of cabozantinib on recombinant CYP2C11 rat isoform has been studied in...
|