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Journal of Medical Oncology & Therapeutics | Volume 4
March 18-19, 2019 | London, UK
Oncology & Cancer Therapy
International Conference on
Radioresistance of breast cancer stem cells after single-dose and fractionated γ-radiation exposure
and radiosensitizing effect of dimeric bisbenzimidazoles
in vitro
Matchuk Olga N, Churyukina K A, Zhuze A L
and
Zamulaeva I A
A Tsyb Medical Radiological Research Center, Russia
N
umerous studies have proven the high resistance
of cancer stem cells (CSCs) to a single-dose low-LET
ionizing radiation exposure in vitro. However, the patterns
and mechanisms of fractionated radiation effects on this
population of cells have not been studied enough. The
aim of the study was to elucidate effects of single-dose
and fractionated γ-radiation exposure on CSCs of breast
adenocarcinoma line MCF-7 and reveal means for CSC radio
sensitization by inhibition of DNA damage repair. CSCs were
isolated as CD44
+
CD24
low/-
cells or side population (SP) by flow
cytometry. Both methods were used to show a statistically
significant increase in the relative and absolute number
of CSCs both after single-dose and fractionated irradiation
at doses of 4 Gy and more. These data were the basis for
further work in order to reduce the resistance of CSCs in
the range of 4-6 Gy. Synthetic dimeric bisbenzimidazoles –
DB(n) that specifically bind to DNA A-T enriched sequences
and inhibit a number of enzymes involved in chromatin
remodeling and repair of DNA damages were synthesized. In
our experiments length of oligomethylene linker (n) between
two bisbenzimidazole blocks ranged from 1 to 11. DB (5) and
DB (7) in combination with irradiation significantly reduced
the proportion and clonogenic ability of CSCs compared with
those after radiation exposure (p<0.05). The coefficients
of the synergistic effect of these compounds and radiation
on CSC clonogenicity were 1.3 for DB (5) and 1.2 for DB (7).
Thus, the results showed that DB (5) and DB (7) could be
used to develop anticancer drugs for elimination of CSCs and
increase the effectiveness of cancer patient radiotherapy.
This work was supported by grant of Russian Scientific
Foundation # 18-75-10025.
Speaker Biography
Matchuk Olga N has completed her PhD fromA. TsybMedical Radiological Research Center,
Russia in 2016. She is senior researcher of Laboratory of Radiation Biochemistry of Medical
Radiological Research Center. She has over 50 publications (in English and Russian) that
have been cited over 90 times, and her publication H-index (Scopus) is 4.
e
:
matchyk@mail.ru