The Expression Of XIAP In Colon Carcinoma And Its Effect On The Sensitivity Of SW620 To Chemotherapy

Objective: colon carcinoma is one of the most frequent malignant tumour in alimentary canal, according to the statistics, there are nearly 40000 people who died of colon carcinoma. Abdominal surgery is one of the important treatment approach with a mortal drawback that the recurrence rate is very high after surgery when the colon carcinoma were in middle or advanced stage, and because it is hard to catch the attention of patient when the colon carcinoma were in preliminary stage, most of the colon carcinoma patients in middle or advanced stage were insensitive to chemotherapeutics and had a bad prognosis. X-linked inhibitor of apoptosis protein(XIAP) is one of the most effective species in the family of apoptosis inhibitor, participates in the proliferation and transformation of many type of malignant tumors, and has close relationship with the chemotherapeutic resistance of carcinoma, further approaching the feasibility of inhibiting the expression of XIAP in the cell of colon carcinoma cell SW620 and illuming the effectiveness of improving the sensitiveness of colon carcinoma cell to chemotherapeutics after inhibiting are the objective of this thesis.Methods: gathering 31 examples of colon carcinoma tissue, 12 examples of latero-carcinoma tissue from normal surgery National Hepatobiliary & Enteric Surgery Research Center between February of 2004 and May of 2006 after exairesising, observing the expression level of XIAP in the tissue of colon carcinoma and latero-carcinoma by the means of histochemical stain, analysing the relationship between the expression level of XIAP and the colon carcinoma patho-ranking, clinical stage. Culturing colon carcinoma cell SW620, inducing the drug resistance of cell to chemotherapeutics applying with the interruption effect of 5-FU with the concentration of 1.0ug/ml and 10ug/ml, detecting the chang of XIAP expression level after inducing through RT-PCR and Western blot, detecting the sensitiveness of cell to the drug of 5-FU between the period of before and after inducing through MMT, and then analysising the relationship between the expression level of XIAP and the drug resistance of cell to chemotherapeutics. Detecting the inhibition efficiency of 5-FU drug to the mRNA and protein of XIAP, overviewing the change of apoptosis index after the inducing of chemotherapeutics by the means of flow cytometry and staining.Result: XIAP expressed both in the tissue of colon carcinoma and latero-carcinoma, the expression rate in colon carcinoma tissue is 26/31 (83.87%), which is apparently higher than that of latero-carcinoma, which is only 5/12(41.6％) (P＜0.01). The expression of XIAP in colon carcinoma is independence with clinical stage(P＞0.05), but concerned with the patho-ranking of colon carcinoma(P＜0.05). The medium effective concentration(IC50) of 5-FU to SW620 rose from 1.327±0.21ug/ml to 1.823±0.107.ug/ml and 2.273±0.035ug/ml, differently after 10 days' interval culturing with 5-FU with the concentration of 1.0ug/ml and 10ug/ml differently, and it rose to 2.273±0.035ug/ml, 5.761±0.254ug/ml and 6.573±0.512 ug/ml (P＜0.01) differently after one month' culturing. The protein contents of XIAP rose lightly after 10 days' culturing, and the mRNA contents did not rise obviously; but after one month' culturing both the mRNA and protein contents of XIAP rose apparently, the expression level of XIAP concerned with the drug resistant of cell to 5-FU(P＜0.01), the high expression of XIAP might participate in the malignant transformation of colon carcinoma.Conclusion: The expression rate of XIAP in colon carcinoma tissue was obviously higher than in latero-carcinoma tissue, the high expression of XIAP might participate in the maligant transformation, generating of proliferation and drug resistance of colon carcinoma. Because 5-FU killed colon carcinoma cell through inducing cell apoptosis, increase the sensitiveness of cell to chemotherapeutics.