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Ann Surg Treat Res. 2017 Jan;92(1):15-22. English. Original Article.
Kim HB , Cho WJ , Choi NG , Kim SS , Park JH , Lee HJ , Park SG .
Department of Premedical Course, Chosun University School of Medicine, Gwangju, Korea.
Department of Urology, Chosun University Hospital, Gwangju, Korea.
Department of General Surgery, Chosun University Hospital, Gwangju, Korea.
Department of Otolaryngology Head and Neck Surgery, Chosun University Hospital, Gwangju, Korea.
Division of Hemato-Oncology, Department of Internal Medicine, Chosun University Hospital, Gwangju, Korea.

PURPOSE: Biliary cancer is a highly malignant neoplasm with poor prognosis and most patients need to undergo palliative chemotherapy, however major clinical problem associated with the use of chemotherapy is chemoresistance. So far, we aimed at investigating clinical implications of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and Jagged1 as chemoresistance factors in biliary tract cancer. METHODS: We used 5 human biliary tract cancer cell lines (SNU-245, SNU-308, SNU-478, SNU-1079, and SNU-1196), and investigated the chemosensitivity of APEX1 and Jagged1 through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Western blot. Alternately, the 10 patients of advanced biliary cancer consist of 2 group according to the chemotherapy response examined by immunohistochemistry using APEX1 and Jagged1 antibody, and protein expression level was scored for staining intensity and percent positive cell. RESULTS: The result of MTT assay after APEX1 knockdown showed that strong coexpression of APEX1 and Jagged1 cell line (SNU-245, SNU-1079, and SNU-1196) showed a greater decrease in IC₅₀ of chemotherapeutic agent (5-fluorouracil, gemcitabine and cisplatin). The Western blot analysis of APEX1 and Jagged1 expression in biliary cancer cell lines after APEX1 knockdown definitively demonstrated decreased Jagged1 expression. The APEX1 and Jagged1expression level of immunohistochemistry represented that chemorefractory patients had higher than chemoresponsive patients. CONCLUSION: These results demonstrate that simultaneous high expression of APEX1 and Jagged1 is associated with chemoresistance in biliary cancer and suggest that is a potential therapeutic target for chemoresistance in advanced biliary cancer.

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