ABSTRACTS – ORAL PRESENTATIONS - AMCA, spol. s r.o.

In summary, our results demonstrated that combination of RGZ with oxaliplatin may be
more effective then single drug treatment in both sensitive and resistant colon cancer
cells. Thus, this combination seems to be promising in the treatment of colon cancer
cells resistant to oxaliplatin.
Acknowledgement
This work was supported by grant of Internal Grant Agency of Ministry of Health of the
Czech Republic No. NT 11201-5/2010, grant Czech Science Foundation No. P301/11/1730
and FNUSA-ICRC European Regional Development Fund No. CZ.1.05/1.1.00/02.0123.
P32. SYNTHETIC LETHALITY OF CHK1 INHIBITION AND DNA DAMAGE IN NORMAL
AND TUMOR CELL LINES
Tereza Suchánková 1 , Ondřej Hylse 2 , Kamil Paruch 2,3 , Zuzana Pernicová 1,3 , Alois Kozubík 1,4 ,
Karel Souček 1,3
1
Academy of Sciences of the Czech Republic, Institute of Biophysics, Královopolská 135,
61265 Brno, Czech Republic.
2
Department of Chemistry, Faculty of Science, Masaryk University, Brno, Czech Republic.
3
International Clinical Research Center, St. Anne‘s University Hospital Brno, Brno, Czech
Republic
4
Department of Experimental Biology, Masaryk University, Faculty of Science, Brno,
Czech Republic.
Correspondence to: suchankovatereza@ibp.cz, ksoucek@ibp.cz
Progress in understanding of the pathways affected by cancer specific mutations lead
to novel therapeutic approach called the concept of synthetic lethality. Components of
DNA damage response pathway were identified as suitable targets of synthetic lethal
interactions with commonly lost tumor suppressor genes such as p53. Loss of tumor
suppressor gene alone may not change the response to genotoxic stress induced by
chemotherapy. However, the inhibition of a second pathway involved in a synthetic lethal
interaction with this lost suppressor can result in a dramatic difference in sensitivity to
treatment. In this context, the promising druggable targets are kinases regulating the
cell cycle checkpoints.
Checkpoint kinase 1 (CHK1) is an essential serine/threonine kinase that responds to
DNA damage. CHK1 inhibitors sensitize tumors to a variety of DNA-damaging agents in
preclinical models and are being evaluated in clinical trials. SCH 900776 was identified as
a potent and selective CHK1 inhibitor (Guzi et al., 2011).
In our work, we proved the hypothesis of synthetic lethality using inhibitors of CHK1 in
combination with pre-treatment by gemcitabine and hydroxyurea in vitro in normal and
tumor cells. Our results indicate that these inhibitors enable to reduce the concentration
of chemotherapeutics to obtain the same growth inhibition. The most significant
sensitization was observed in human prostate cancer cell lines PC3 and DU-145. The
effect was also achieved in tumorigenic prostate cells BPH-1 CAFTD03, but only transient
effect has occurred in their benign counterparts. Further, using the same amount of drug
Analytical Cytometry VII 125