| A new cell culture models of urothelial carcinoma links mitochondrial physiology to multidrug resistance.
Kripnerova M, Markova M, Hatina J, Kuncova J (2017)
Urothelial bladder carcinoma is a very heterogous group of cancers with about 430 000 affected people worldwide yearly. Resistance to apoptosis is a frequent property of cancer cells and participates both in the initial phase of carcinogenesis and in the development of chemoresistance. Resistant tumor cells can acquire an ability to evade the action of multiple classes of various anti-cancer drugs. In order to better understand the processes underlying clinical chemoresistance, we developed a new cell culture model consisting of two clonally related cell lines – BC44 and BC44DoxoR. The parental cancer cell line BC44 has been established from the large exophytic and better differentiated papillary part of a progressive urothelial bladder cancer from a female patient. We derived a daughter multidrug resistant cell line - BC44DoxoR - by prolonged culture in increasing Doxorubicin concentrations. Remarkably, in spite of being derived by virtue of its resistance to a single cytostatic, this derivative cell line BC44DoxoR exhibited chemoresistance to all cytostatics used in the standard systemic chemotherapy (Doxorubicin, Methotrexate, Vinblastine, Cisplatin and Gemcitabine). In addition, its proliferative activity was distinctly inferior to BC44 parental cell line. The mitochondrial respiration of highly sensitivity cell line BC44 was more effective than the respiratory chain of BC44DoxoR cell line and the physiological respiration of the resistance cell line was very similar to the theoretical maximum utilization of oxygen and showed a very small capacity reserve. We thus conclude that relative quiescence due to a partial mitochondrial functional diminution contributed to the observed multidrug resistance. We believe that BC44 and BC44DoxoR cell lines represent a unique system for understanding of molecular and biological mechanisms and differentially expressed genes underlying the resistance of a tumor. These differentially expressed genes could be important as prognostic and predictive clinical markers, or as a new therapeutic target in urothelial carcinoma.
• Bioblast editor: Kandolf G
• O2k-Network Lab: CZ Pilsen Kuncova J
Labels: MiParea: Pharmacology;toxicology
- Kripnerová M(1), Marková (M), Hatina J(1), Kuncová J(2)
- Dept Biology
- Dept Physiology; Charles Univ Prague-Faculty Medicine Pilsen, Czech Republic. - Michaela.Kripnerova@lfp.cuni.cz