Alterations Of Vegf, Mmp-9 And Caspase-3 Expression In Colonic Tumors Induced By 1, 2-dimethylhydrazine (DMH) In Rats | 12236
Journal of Biotechnology & Biomaterials
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Rationale: 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats is a reliable model to explore molecular
mechanism involved in progression of colorectal cancer from adenoma to carcinoma sequence.
Objective: To study the transcriptional and translational levels of various genes involved in tumorigenesis pathway of DMH
induced rat model.
Methods: Two groups of chow-diet-fed, male Sprague Dawley (SD) rats, aged 10 weeks (n=12/group) were fed a normal diet
and injected subcutaneously for two time durations of 10 and 20 weeks DMH at a dose of 30mg/kg body wt/week or with
Ethylene diamine tetra-acetic acid (EDTA)-saline. Macroscopic and microscopic analyses were performed for confirmation
of adenoma and carcinoma. mRNA expression of VEGF, MMP-9 and Caspase-3 genes were determined by Real-Time PCR.
Immunohistochemistry was also performed for expression of above proteins.
Results: Gross examination of 10 weeks DMH treated colon showed polypoid lesions and multiple tumors after 20 weeks of DMH
treatment. Histopathological studies confirmed the colon carcinogenesis from adenoma-carcinoma sequence by type of tumor,
degree of differentiation & invasion of tumors. In adenomatous and carcinomatous colonic tissues, mRNA expression of VEGF
(3.2 and 5.4 fold respectively) and MMP-9 (2.3 and 8.2 fold respectively) was augmented, whereas expression of Caspase-3 was
reduced by 13.2 and 4.5 fold respectively. These results were confirmed by Immunohistochemistry analysis.
Conclusion: The observed data strongly implicates that DMH induced colon carcinogenesis altered the apoptotic machinery by
modulating the expression of various genes involved in this pathway.
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