الفهرس 
Literature ReviewOnly 14 pages are availabe for public view
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Abstract
Cancer is a class of disease involving abnormal cell growth with the
potential to invade or spread to other parts of the body in a process called
metastasis. Colon and rectum cancer is the third most commonly diagnosed cancer
in males and the second in females, and it is the second leading cause of cancer
death in developed countries.
There is an association between type 2 diabetes mellitus and increased
cancer risk especially in colon, liver and endometrium. Several studies showed a
relation between type 2 diabetes mellitus and increased risk and mortalities of
colorectal cancer. In type 2 diabetes insulin resistance, higher insulin levelsin
blood and tissues, higher levels of insulin like growth factor 1 and its receptor in
tissues can increase cell proliferation and consequently increase cancer risk.
Different studies revealed that patients with type 2 DM who are treated with
metformin had lower incidence of cancers than those treated with other diabetic
drugs.
Aim of the work
This study aimed to investigate the possible anti-cancer effect of metformin in
mice and to find if its role is in diabetic mice only or in both diabetic and nondiabetic
Materials
(1) Mice used in the study were obtained from the modern veterinary office for
laboratory animals (Cairo, Egypt).
(2) 1, 2 dimethlhydrazine was used to induce colon cancer in mice.
(3) Streptozotocin was used for induction of type 2 diabetes mellitus in mice.
(4) Oxaliplatin was used as adjuvant chemotherapy in addition to metformin.
2-Methods
(1) Determination of serum levels of VEGF using ELISA in both non-diabetic
and diabetic mice. Results showed that in non-diabetic mice all implemented
therapies were able to reduce VEGF levels compared to non-diabetic/DMH
control. In diabetic mice monotherapy with metformin (100-200 mg/kg) and
its combination with Oxaliplatin decreased serum level of VEGF compared to
diabetic DMH group. However, monotherapy with Oxaliplatin failed to
produce a similar effect.
(2) Estimation of insulin resistance. Results obtained from experiment II
indicated that the current model of type 2 diabetes mellitus was accompanied
by higher HOMA-IR index compared to mice fed with basal diet in
experiment I.
(3) Histopathological examination of colon tissue by staining with H&E to show
changes in cell size and inflammatory reactions. Tissue sections stained then
viewed using light microscope; it showed that there is a significant difference
in Histopathological score between diabetic/ DMH group and non-diabetic
/DMH group. In non-diabetic mice none of the implemented therapies
reduced the histopathologic score compared to the DMH control while in
diabetic mice all the implemented agents successfully ameliorated the
histopathologic score compared to the DMH control.
(4) Determination of tissue IGFR-1 using immunohistochemically. Statistical
analysis revealed that combination therapies produced a significant decrease in expression of IGFR-1 compared to DMH control in experiment I, while in experiment II monotherapy with Oxaliplatin or metformin 200 mg/kg as well as the two combination therapies produced significant decrease in the immunoreactivity for IGFR_! In colon tissues compared to diabetic DMH control group.
(5) Determination of CD34 expression using immunohistochemistry. In
experiment I immunoreactivity for CD34 in Oxaliplatin, metformin (100
mg/kg) treated groups and the two groups treated with combination therapies was significantly lower than that of the non-diabetic DMH control. In experiment II all the implemented therapies reduced the optical density for CD34 compared to the diabetic DMH control.
(6) Determination of Ki-67 expression. In both diabetic and non-diabetic mice all the implemented therapies showed a decrease in cell proliferation compared with DMH control groups. However, in experiment II mice treated with
metformin (200 mg/kg) and mice treated with Oxaliplatin + metformin (200mg/kg) showed a significantly lower count of Ki-67 stained nuclei compared to Oxaliplatin treated mice.