الفهرس 
Introduction and Aim of The WorkOnly 14 pages are availabe for public view
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Abstract
The understanding of the fundamental role of angiogenesis and
metastasis in cancer growth has led to tremendous interest in research
regarding its regulatory mechanisms and clinical implications in the
management of cancer. The present study was conducted to evaluate the
influence of the angiogenic regulators modification on the tumor growth and
the cell sensitivity to ionizing radiation targeting the improvement of cancer
therapeutic protocols.
Accordingly, the antiangiogenic activity of apigenin and selenium was
tested in vitro as well as in vivo. EAC viability alteration was observed in the
EAC cells incubated with different concentrations of Apigenin and or Selenium
by MTT viability test in vitro, a line of Ehrlich Ascites Carcinoma (EAC) cells
was irradiated at 7 Gy . the action of Apigenin and or Selenium was examined
in vivo in mice bearing Ehrlich cells and or irradiated mice bearing Ehrlich
cells (a model of solid carcinoma tumor). Solid tumors were produced by
intramuscular inoculation in the right thigh of the lower limb of each mouse
with 0.2 ml of EAC cells. The growth rate of solid tumor in all experimental
groups was measured by Caliper. Mice whole body irradiated with 6.5 Gy, The
dose rate was 0.46 Gy/min .
The levels of angiogenic activators were measured such as the
expression of TNFα in spleen, serum MMP-2 &9 zymography and nitric oxide
in liver and tumor tissue . also the expression of spleen TIMP-1 the angiogenic
inhibitor was obtained. as well as the liver and tumor lipid peroxidation
,antioxidant markers (GPx , SOD and CAT) and DNA fragmentation in
splenocytes were estimated to monitor efficacy of apigenin and selenium in
cancer treatment strategy. All parameters were determined as a time course on
days 16 and 22 after tumor volume reached 1mm3. The results obtained were statistically analyzed and can be
summarized as follows:
1- Maximal inhibitory concentration values of Apigenin and sodium
selenite were reached for approximately 80 μg/ml and 5μg respectively,
after 24 h incubation. However, when we treat the cells with 30 μg
Apigenin and 5μg sodium selenite simultaneously, we observed a
synergistic anti proliferative effect. sodium selenite and Apigenin
combination induced cell growth inhibition reached about (81%) .The
radiation exposure of EAC cells treated with Apigenin (30μg) and
sodium selenite (5μg ) showed dramatic cell growth inhibition 90% .
2- A significant induction of TNF-α expression (1086, 1580 and 2040 %,
respectively; P<0.05at the 1st experimental interval) was observed in
samples isolated from the spleen of R , E or E+R mice groups with
substantial increases on the 2ed experimental interval ( 1667, 2173 and
2646 % respectively at P<0.05).The pretreatment with Ap, Se or Ap+ Se
of mice bearing tumor and irradiated mice bearing tumor induced
remarkable modulation in TNF-α gene expression compared to TNF-α
gene expression in Ehrlich bearing mice or irradiated however a minor
effect was recorded on the 2nd experimental interval.
3- Significant induction of MMP2 concentration (183 , 131 and 272%,
respectively; P<0.05at the 1st experimental interval) was observed in
samples isolated from the serum of R , E or E+R groups of mice with
substantial increases at the 2nd experimental interval ( 373 ,271 and 338
% respectively at P<0.05).The pretreatment with Ap, Se or Ap+ Se of
mice bearing tumor and irradiated mice bearing tumor induced
remarkable modulation in MMP2 concentration as compared to MMP2
concentration in Ehrlich bearing mice or irradiated however a minor
effect was recorded on the 2nd experimental interval. Significant induction of MMP9 concentration (201 ,92 and 127%,
respectively; P<0.05at the 1st experimental interval) was observed in
samples isolated from the serum of R , E or E+R groups of mice with
substantial increases at the 2nd experimental interval ( 383 ,139and 280
% respectively at P<0.05).The concentration of MMP9 was
significantly reduced in mice treated with Ap, Se or Ap+ Se before
exposure to gamma irradiation. Furthermore, MMP9 concentration
down regulated in E+R mice group pretreated with Ap, Se or Ap +
Se.the result obtained revealed that Ap + Se combination showed
obvious decrease in serum MMP9 concentration than Apigenin or
selenium alone .
5- Significant reduction of TIMP-1 expression (49-,63- ,77- %,
respectively; P<0.05at the 1st experimental interval) was observed in
samples isolated from the spleen of R , E or E+R groups of mice with
substantial decreases at the 2nd experimental interval ( 63-,76-,55- %
respectively at P<0.05).The pretreatment with Ap, Se or Ap+ Se of mice
bearing tumor and irradiated mice bearing tumor induced remarkable
increase in TIMP-1 gene expression as compared to TIMP-1 gene
expression in Ehrlich bearing mice. However a minor effect was
recorded on the 2nd experimental interval .
6- Significant induction of NO concentration (97, 65 and 103 %,
respectively; P<0.05at the 1st experimental interval) was observed in
samples isolated from the liver of R , E or E+R groups of mice with
substantial increases at the 2nd experimental interval ( 109 ,95 and 133 %
respectively at P<0.05).The concentration of NO was significantly
reduced in mice treated with Ap, Se or Ap+ Se before exposure to
gamma irradiation. Furthermore, NO concentration down regulated in
E+R mice group pretreated with Ap, Se or Ap + Se. the result obtained
revealed that Ap + Se combination showed more obvious decrease in
liver NO concentration than Apigenin or selenium alone .Whole body gamma irradiation to mice bearing tumor induced high increase of NO
concentration in tumor tissue . This increase was more evident on 2nd
experimental interval. Treatment with Apigenin and or Selenium before
irradiation of mice bearing Ehrlich induced significant increase of NO
concentration in tumor tissue when compared to its corresponding value
in E +R mice .the result obtained revealed that Ap + Se showed
obvious increase of NO concentration in tumor tissue than Apigenin or
selenium alone. Whole body Gamma irradiation of mice bearing a tumor and treated
with apigenin and / or selenium for 14 days shows a marked reduction
in tumor volume at 16 days, and a further significant suppression at 22
days, compared to that in the non treated mice bearing Ehrlich. the (E
+AP + Se +R) mice reveal the most reduced tumor volume as compared
with other groups.
8- Significant induction of TBARS concentration (93 , 130 and 183 %,
respectively; P<0.05at the 1st experimental interval) was observed in
samples isolated from the liver of R , E or E+R groups of mice with
substantial increases at 2nd experimental interval ( 125 ,153 and 199
respectively at P<0.05).The concentration of TBARS was significantly
reduced in mice treated with Ap, Se or Ap+ Se before exposure to
gamma irradiation. Furthermore, TBARS concentration was down
regulated in E+R mice group pretreated with Ap, Se or Ap + Se.Whole
body gamma irradiation to mice bearing tumor produce more noticeable
increase of TBARS concentration in tumor tissue. This increase was
more evident on 2nd experimental interval.Treatment with Apigenin,
Selenium or Apigenin +Selenium before irradiation of mice bearing
Ehrlich induced significant increase of TBARS concentration in tumor
tissue when compared to its corresponding value in E +R mice.The Ap
+ Se mice have a most tumor TBARS level increment compared to
Apigenin or selenium alone.