Resistance to anti-cancer drugs is a well recognized problem and very often it is responsible for failure of the cancer treatment. In this study, the proteome alterations associated with the development of acquired resistance to cyclin-depedent kinases inhibitor bohemine, a promising anti-cancer drug, were analyzed with the primary aim of identifying potential targets of resistance within the cell that could pave a way to selective elimination of specific resistant cell types. A model of parental susceptible CEM T-lymphoblastic leukemia cells and its resistant counterpart CEM-BOH was used and advanced 2-D liquid chromatography was applied to fractionate cellular proteins. Differentially expressed identified proteins were further verified using immunoblotting and immunohistochemistry. Our study has revealed that Rho GDP-dissociation inhibitor 2, Y-box binding protein 1, and the HSP70/90 organizing protein have a critical role to play in resistance to cyclin-depedent kinases inhibitor. The results indicated not only that quantitative protein changes play an important role in drug-resistance, but also that there are various other parameters such as truncation, post-translational modification(s), and subcellular localization of selected proteins. Furthermore, these proteins were validated for their roles in drug resistance using different cell lines resistant to diverse representatives of anti-cancer drugs such as vincristine and daunorubicin.

• MeSH
• antitumorózní látky farmakologie   MeSH
• biologické modely MeSH
• chemorezistence MeSH
• DNA vazebné proteiny metabolismus   MeSH
• imunoblotting MeSH
• inhibitory disociace guaninnukleotidů metabolismus   MeSH
• jaderné proteiny metabolismus   MeSH
• lidé MeSH
• mapování interakce mezi proteiny MeSH
• nádorové buněčné linie MeSH
• nádorové supresorové proteiny metabolismus   MeSH
• protein 1 vázající Y-box MeSH
• proteiny tepelného šoku metabolismus   MeSH
• proteom analýza   metabolismus   MeSH
• puriny farmakologie   MeSH
• spektrofotometrie ultrafialová MeSH
• subcelulární frakce metabolismus   MeSH
• výpočetní biologie MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH