The Expression of HMGB1 in Colorectal Cancer and SW620 Cells ...

[Abstract]

Background:Colorectal cancer is a major malignancy in China. In recent years, the incidence of colorectal cancer has showed an upward trend, this trend is obvious in large and medium-sized cities. However, the molecular mechanisms leading to the occurrence and progression of colorectal cancer remain elusive. Recent research has found that there are a multi-step mutation of the oncogene and tumor suppressor gene(TSG)inactivation in the occurrence of colorectal cancer, at the same time, with a large number of abnormal protein expression. So, one major challenge in colorectal cancer research is the identification and characterization of relevant expression products of tumor protein. This experiment majorly studies the relation between HMGB1 and the colorectal cancer.HMGB1 was a widely existed DNA-binding protein when it was firstly discovered. It participates in DNA transcription, replication, repair, and the movement of cells. With the in-depth research, HMGB1 could be used as a cytokine, it can be released from macrophages, monocytes by the stimulation of LPS, IL-1, TNF. HMGB1 can also be released from damaged or necrotic cells, and it combines with RAGE(receptor for advanced glycation end products), a cell surface receptor, involving in cell differentiation and maturation.HMGB1 is over-expressed in many tumors and the level is much higher than the corresponding normal tissue, moreover, it related to the invasion and metastasis of many tumors. In vivo, the migration of cells heavily rely on the capacity of invading surrounding tissue, then the activation of extracellular kinase is necessary. HMGB1 can combine with several components of plasminogen activation system, improving the activation of t-PA. And HMGB1 can also activate MAPK, P38MAPK, JNK and P42/P44MAPK signaling pathway by combining with RAGE , then causing the activation of matrix metalloproteinase MMP22 and MMP29. They are two downstream targets of plasmin cascade activation, moreover, they could degradate extracellular matrix and promote tumors?invasion and metastasis. In addition, HMGB1 may act as an antiapoptotic oncoprotein.HMGB1 increased NK-?B activity and lead to co-expression of antiapoptotic NK-?B target gene product c-IAP2 in vitro.Furthermore,increased HMGB1 levels correlated with enhanced amounts of c-IAP2.Finally,we demonstrated that HMGB1 overexpression surpressed caspase-9 and caspase-3 activity,suggesting that HMGB1 interfers with the apoptotic machinery at the level of apoptosomal caspase-9 activation.In addition, the current study shows that in the normal cells, cancer cells and mouse macrophage cells, SB can block cytokines and LPS-mediated inflammatory response by inhibiting NF-?B signal transduction pathway. Previous information confirm that NF-?B is closely related to multiple organ dysfunction in sepsis, and NF-?B signal transduction pathways involved in the control of LPS-mediated gene expression of HMGB1, in addition, NF-?B inhibitors can significantly inhibit the expression of HMGB1mRNA in endotoxic shock animal. Therefore, we speculate that SB inhibiting NF-?B signal transduction pathway may be an important way of preventing the release of HMGB1.Objective:1?To investigate the expression of high mobility group box1(HMGB1)in human colorectal cancer and explore its relationship to tumor size, differention and metastases of human colorectal cancer; 2?Training SW620 cell lines and observing the HMGB1 expression in SW620 cells, as well as different drug concentration on the impact of the proliferation of cancer cells by adding different concentrations of SB, thereby exploring the relationship between HMGB1 and colorectal cancer cell proliferative activity.Methods:Immunohistochemistry is used to detect the expression of HMGB1 in 70 colorectal cancer tissues, 70 juxtacancerous tissues and 70 normal colorectal tissues. Training SW620 cells, using MTT to assay the proliferation of SW620 cell between different experimental groups and control group, calculating inhibition rate, drawing the curve of inhibition rate;and observing HMGB1 protein expression between different experimental groups and control group by immunocytochemistry.Results:HMGB1 is strongly expressed in colorectal cancer tissues(80.0%), only very low expression is found in juxtacancerous tissues, and no expression is found in normal colorectal tissues. HMGB1 is found to be significantly correlated with tumor size, regional invasion, and lymphatic and blood stream metastasis(P 0.05); by adding different concentrations of SB, the growth of SW620 cells is inhibited in every experimental groups, and the inhibition of SB shows a certain time-and-drug dependent relation ; Meanwhile, with the increase of drug concentration, the expression of HMGB1 also declines.Conclusions:HMGB1 in colorectal cancer showes strong expression,in addition,HMGB1 is closely linked to the metastasis and proliferation of colorectal cancer,it can be used as the important judgment indicators of colorectal cancer growth, metastasis and prognosis.

Title: The Expression of HMGB1 in Colorectal Cancer and SW620 Cells and Its Significance

Category: Pituitary Tumor

Filename: The Expression of HMGB1 in Colorectal Cancer and SW620 Cells and Its Significance.pdf

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