الفهرس 
TitleOnly 14 pages are availabe for public view
 |  | from | 91 |  |  |
| | | from | 91 | | |
Abstract
HSPs are important regulators of cellular proliferation, diversity and sturdy involved in
the molecular orchestration of most cancer enhancement and development as many of their
consumers are properly established oncoproteins in several tumor kinds. Excitingly, tumor
cells are extra Heat shock proteins chaperonage-reliant on than usual cells for spread and
survival due to the fact the oncoproteins in cancer cells are many regularly misfielded and
need increased chaperonage action for alteration.
The most studied strain-inducible HSPs are HSP90, HSP70 and HSP27. The expression
and/or action of these 3 HSPs is unusually excessive in most cancer cells and more
accelerated after death stimuli. They are strong anti-apoptotic proteins, relating with the main
apoptotic factors.
The current study aims to explore whether Heat shock proteins 27, 70 and 90 exert their
action in breast cancer cells resistance to radiation through abrogating the apoptotic pathway
of cell death.
Human BC cell lines MCF-7 and MDA-MB-231 culture, each of which was divide into
four groups:
group 1: Cells were exposed to radiation (at doses 0, 4, 6, 8 and 10 Gy).
group 2: Cells were treated by Quercetin HSPs inhibitor at concentration 15 and 50 μMol
group 3: Cells were exposed to a combination of Quercetin at concentration 15 and 50
μMol and radiation at doses 4, 6, 8 and 10 Gy.
group 4: Cells were grown without treatment by Quercetin or radiation.
Our results showed that:
HSF-1 expression was significantly reduced in response to treatment by quercetin,
while in the control group it was significantly increased in response to radiation
exposure.
Both HSP-70 and HSP-27 significantly increased in response to radiation in controls
of both cell lines and to a lesser extent HSP-90 too.
Treatment by quercetin alone resulted in a significant dose-dependent up-regulation
of caspase-3 expression in MDA-231 cells but not in MCF-7 cells. Upon the shared
treatment of cells by both radiation and quercetin, MCF-7 cells retained caspase-3
down-regulation at all radiation doses while MDA-231 cells showed a significant upregulation
that increased with increasing quercetin concentration.
STAT-3 expression in MCF-7 was up-regulated at lower radiation doses (4 and 6
Gy), while higher radiation doses resulted in its partial inhibition. Meanwhile, in
MDA-231 cells, STAT-3 was down-regulated in response radiation at all doses.
Quercetin treatment resulted in a significant dose-dependent up-regulation of STAT-3
expression in the two cell lines.
Summary, Conclusion & Recommendations
62
When exposed to radiation alone, MDA-231 cells showed a significant downregulation
in p21 expression, but not MCF-7 cells. But upon treatment with quercetin,
MCF-7 cells showed a significant down-regulation, while MDA-231 cells showed a
significant up-regulation of p21 expression levels.
Exposure to radiation resulted in a significant decrease in survival in both cell lines in
a dose-dependent manner, with MCF-7 showing significantly lower survival than
MDA-231 cells. Treatment by quercetin alone resulted in a significant reduction in
survival of MCF-7 cells at 15 μMol and in MDA-231 starting at 50 μMol. Exposure
to both quercetin and radiation resulted in lower survival than radiation alone.