| Colorectal cancer is one of the most common malignant tumors in the world, new caseseach year about8million people around the world, and the incidence rates have increasedyear after year. the ability of invasion and metastasis is one of the important factors leading topoor prognosis of patients. So investigating the mechanisms of the tumor invasion andmetastasis,which can improve the prognosis of patients with colorectal carcinoma hasimportant clinical value.Solid tumors in the process of growing, the center will form a hypoxic microenvironment. Itcan lead to tumor cells appear many biological characteristics change, the epithelial-mesenchymaltransition is an important phenotypic change. Always for EMT research mainly focused on avariety of hypoxia inducing factors mediated gene transcription activation downstream link, inand of itself cannot be directly feel the change of oxygen partial pressure. And PHD2is one ofthe important of oxygen sensors found in recent years, can be directly regulate cell responseto oxygen concentration change ability, is the real feel directly molecular oxygen partialpressure. Has now been confirmed in mammalian cells there are three analogues--PHD1、PHD2and PHD3, and studies have found that PHD2expressed in a variety of tumor cell linesor tumor tissue loss. Its relationship with the invasion and metastasis of tumor has not beenreported so far.This research proposed by studying PHD2in colorectal cancer tissues and colorectalcancer metastases in the expression and clinical pathological features of the organization andthe relationship between tumor invasion and metastasis, and through the experiments furtherclarify its correlation with the invasion and metastasis of colorectal carcinoma cells in vitro.To provide a new direction for further anti-tumor treatment.Objective: To detect the expression of PHD2in colorectal carcinoma tissues andmetastases, discuss its clinical significance, preliminary studies how it can regulate EMT andthe migration and metastasis of colorectal cancer cells.Methods: Colorectal cancer tissues, corresponding metastases as well as5colon cancer cell lines (SW-480、SW-620、LS174T、SW-480mock and SW-480over) were used.This work includes two parts.Part Ⅰ: Immunohistochemical assay of PHD2expression in tissue microarray composedof149colorectal carcinoma tissues and50cases of colon carcinoma metastases was carriedout, investigating the relationship between PHD2protein expression in colorectal cancertissues and clinical pathological features, following the analyses of the relationship betweenPHD2expression and the invasion and metastasis of colorectal carcinoma cells.Part Ⅱ: Using Western blot and lentivirus transfection method, detecting the expressionof PHD2protein in SW-620、SW-480、LS174T、SW-480mock and SW-480over cell lines,through transwell experiment to observe its relationship with the migration ability of tumorcells.Results:1、The expression of PHD2down-regulates or loses in colorectal cancer tissues, andincreases in the intestinal mucosa tissue adjacent to carcinoma, and with tumor clinical stages(P<0.001), tumor differentiation degree (P <0.001) and metastasis are closely related. Theexpression of PHD2in colorectal carcinoma the corresponding metastases is lower thanprimary tumors (P<0.05).2、 The expression of PHD2in three kinds of colorectal carcinoma cell lines is inverselywith the invasive ability, And after the overexpression of PHD2protein, cell migration abilitydecreased obviously.Conclusion:1、Differences between PHD2expression in colorectal cancer, closely related to thedifferentiation and clinical stage and metastasis of tumor, And PHD2expression in colorectalcancer the corresponding metastases is lower than primary tumors, Prompting PHD2mayplay an important role in malignant colorectal cancer development.2、PHD2high expression significantly inhibit colorectal cancer cell lines after migrationability, Prompting PHD2and migration is closely related to the invasive ability of colorectalcancer. |
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