| Background and objective:Colorectal cancer is a common malignant tumor in digestive tractor, the exact mechanisms of which still remain unknown. As early as in 1931,Otto Warburg found the phenomenon of enhanced glycolysis and decreased aerobic oxidation of glucose in tumours, but increasingly importance was attached to the role and mechanism of abnormal energy metabolism in tumorigenesis and tumor progression until recent years.Recent studies have found that succinate dehydrogenase is a tumor suppressor encoded by nuclear gene, which provided an important clue to the study of the triggers of enhanced glycolysis.And it was the first time to associate mitochondrial enzymes and their dysfunction with tumorigenesis.Further research forward showed that succinate, which accumulate in mitochondria owing to the inactivation of SDH, leak out to the cytosol,where they inhibit a family of prolyl hydroxylase enzymes (PHDs).Depending on the PHD inhibited, affected tumor cells become resistant to certain apoptotic signals and/or activate hypoxia-inducible factor (HIF),which result in the tumor formation and maintenance. There is no related literature regarding the role of SDH in tumor occurrence and maintenance in colorectal cancer domestic and abroad. This research was to study the expression of SDH in colorectal cancer and analyze the relationship among its expression, clinicopathological characteristics and prognosis, and analyze the relationship between SDH and HIF-1α, which lay a foundation for further study of the mechanism of SDH in colorectal cancer.Methods:In the present study, the expression of the protein level of the four subunits of SDH(SDHA,SDHB,SDHC and SDHD)were examined in 336 colorectal tissue cores using tissue microarray analysis by immunohistochemical analysis.Further analysis was performed to clarify the relationship between the protein expression, clinicopathological parameters and prognosis. Meanwhile, the expression of SDHB and HIF-la were analyzed by western blot in three colon cancer cell lines and colon cancer tissues with different differentiation status.Results:(1)Immunohistochemistry assay revealed decreased expression levels of SDHB in colorectal cancer compared with the adjacent mucosa and adjacent normal mucosa of primary tumor, while no significant difference was found in the expression level of SDHA, SDHC and SDHD in colorectal cancer and normal mucosa. Moreover, a close association was observed between SDHB expression and the tumor differentiation grade. The expression level of SDHB significantly reduced in poorly differentiated colorectal cancer than moderately differentiated and well-differentiated colorectal cancer. Western blot showed similar result.(2)There was no activated HIF-1αexpression in colorectal cancer tissues with differencial SDHB expression level.SDHB protein is high expressed in HT-29 cell line but not in SW480, SW620 cell lines.No activated HIF-1αprotein expressed could be detected in all these three cell lines in normoxia. However, western blot assay showed cobalt chloride could induce the expression of activated HIF-la protein. (3) Survival analysis revealed that "age", "Duke's stage", "distant metastasis" and "lymph node metastasis" were closely related with the prognosis of patients with colorectal cancer. While no correlation between the expression of SDHB and the prognosis was found at present.Conclusion:(1)In this research, the expression level of four subunits of SDH was firstly studied in colorectal cancer. Colorectal cancer and normal mucosa showed high expression levels of SDHA, SDHC and SDHD, and there was no significant difference in the level of protein expression among colorectal carcinoma, adjacent mucosa and adjacent normal mucosa of primary tumor. The expression level of SDHB protein decreased in colorectal cancer as compared with normal colorectal mucosa. The expression of SDHB decreased more severely in poorly differentiated colorectal cancer than in moderately differentiated and well-differentiated colorectal cancer. No correlation between the expression of SDHB and the prognosis was found at present. (2) Survival analysis revealed that "age","Duke's stage","distant metastasis" and "lymph node metastasis" are closely related with the prognosis of patients with colorectal cancer.
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