APA
Gutiérrez-González, Alejandra & Belda-Iniesta, C. & Bargiela-Iparraguirre, J. & Dominguez, G. & García Alfonso, P. & Perona, R. & Sanchez-Perez, I. .Targeting Chk2 improves gastric cancer chemotherapy by impairing DNA damage repair.
ISO 690
Gutiérrez-González, Alejandra & Belda-Iniesta, C. & Bargiela-Iparraguirre, J. & Dominguez, G. & García Alfonso, P. & Perona, R. & Sanchez-Perez, I.. Targeting Chk2 improves gastric cancer chemotherapy by impairing DNA damage repair.
https://hdl.handle.net/20.500.12080/44942
Resumen:
Our results demonstrate that the addition of
cisplatin after paclitaxel-induced mitotic arrest was more
effective than individual treatment on gastric adenocarci noma cells (MKN45). However, the treatment did not
induce benefits in cells derived from lymph node metas tasis (ST2957). Time-lapse microscopy revealed that cell
death was caused by mitotic catastrophe and apoptosis
induction, as the use of the caspase inhibitor z-VAD-fmk
decreased cell death. We propose that the molecular
mechanism mediating this cell fate is a slippage suffered by
these cells, given that our Western blot (WB) analysis
revealed premature cyclin B degradation. This resulted in
the cell exiting from mitosis without undergoing DNA
damage repair, as demonstrated by the strong phosphory lation of H2AX. A comet assay indicated that DNA repair
was impaired, and Western blotting showed that the Chk2
protein was degraded after sequential treatment (paclitaxel cisplatin). Based on these results, the modulation of cell
death during mitosis may be an effective strategy for gas tric cancer therapy.
Keywords Cancer ! Mitosis ! Cisplatin ! DNA damage
response