The Expression And Significance Of XIAP And Its Effect On The Sensitivity To Chemotherapeutics After Inhibited By RNAi In Pancreatic Carcinoma

Objective Pancreatic carcinoma is one of the most common and poorest prognosis abdomen malignant tumour with a high intrinsic potency to develop chemoresistance. The x-linked inhibitor of apoptosis (XIAP), as the most potent one of inhibitor of apoptosis (IAP) families, up-regulating in many cancer tissues and cells, is thought an important factor contributed to carcinoma proliferation, transformation and chemoresistance. To elucidate the expression of XIAP in pancreatic carcinoma tissues and cell SW1990, and further investigate its relationship to the pathological grade and clinical stage, and the relationship between it's expression and the chemoresistance. Then the possibility of XIAP inhibited by RNA interference (RNAi) vectors explored, and the sensitivity to chemotherapeutical drugs changed of pancreatic carcinoma cells SW1990 after XIAP inhibited.Method 23 Samples of resected pancreatic carcinoma tissue and 12 tissues from the carcinoma besides from January 2002 to June 2004 in Xiangya hospital examined by immunohistochemistry and the relationship of XIAP expression to the clinical stage and pathological grade analyzed. The pancreatic cell line SW1990 cultured by RPMI1640, and the 5-FU with the concentration of 1 μg /ml and 10 μg /ml used interval to increase the chemoresistant capability of SW1990 pancreatic cell line, and XIAP expression examined by RT-PCR and Western blot, then the sensitivity of SW1990 to chemotherapeutical drug further examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and the XIAP level of the cell and its chemoresistance to 5-Fu analyzed by linear regression. RNA interference vectors with H1 promoter against XIAP constructed and transfected into the pancreatic carcinoma cell line SW1990, the expression of XIAP determined by RT-PCR and Western blot, and FCM and Hoechst 33258 staine employed to examine the apoptosis index of SW1990 induced by GEM or 5-Fu.Result XIAP expressed in 20 of 23 (86.9%) of pancreatic carcinoma tissues, and 4 of 12 (33.3%) of carcinoma besides tissues (P<0.01); the XIAP level of carcinoma tissues higher than the carcinoma besides...