title: Effect of the GLP-1 analog exendin-4 and oxaliplatin on intrahepatic cholangiocarcinoma cell line and mouse model.
abstract: The influence of Glucagon-like peptide-1 (GLP-1) and Exendin-4 on development of intrahepatic cholangiocarcinoma (ICC) is evaluated in the study. In vitro tests, including acute toxicity test, cell colony formation assays, cells proliferation and apoptosis, transwell assay, were performed. An ICC in situ tumor animal model was established. Then, animals were randomly divided into four groups (n = 6): control, Exendin-4 treatment, oxaliplatin treatment and Exendin-4-oxaliplatin treatment. Animals in the Exendin-4 treatment and Exendin-4-oxaliplatin treatment groups received a subcutaneous injection of Exendin-4 (100 μg/kg/day) for 1 week, and then received oxaliplatin (10 mg/kg/week) by tail vein injection. Animals in the control group received PBS. Immunohistochemistry tests were used for PCNA, Ki67, Caspase 3 expression in tumor tissue. Results show that that, after incubation of human cholangiocarcinoma cell lines, HuCCTI and GLP-1, or HuCCTI and Exendin-4, colony formation number was sharply decreased. However, GLP-1, HuCCTI or Exendin-4 did not affect the colony of normal cells. Combination treatment with oxaliplatin and Exendin-4 can significantly inhibit tumor cells' proliferation and promote apoptosis. The combined effect is stronger than that of oxaliplatin or Exendin-4. Combination treatment with oxaliplatin and Exendin4 can significantly decrease Ki67 and PCNA proteins' expression in subcutaneous tumors of nude mice. The inhibitory effect of Combination treatment with oxaliplatin and Exendin4 is clearly stronger than that of oxaliplatin. In addition, Combination treatment with oxaliplatin and Exendin4 can significantly increase Caspase3 protein positive expression. In short, these results show that combination treatment with oxaliplatin and Exendin4 can inhibit tumor cells' proliferation, and promote apoptosis.
authors.forename: Ben-Dong
authors.initials: BD
authors.lastname: Chen
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Zhao
authors.forename: Qing-An
authors.initials: QA
authors.lastname: Jia
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Bu
authors.forename: Zuo-Zheng
authors.initials: ZZ
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Wu-Jun
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, Ningxia Medical University, Yinchuan 750004, Ningxia, China. wangqnxmed@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D000077150:Oxaliplatin; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D023382:Toxicity Tests, Acute; D014183:Transplantation, Heterologous; D014688:Venoms / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019394:Ki-67 Antigen; D009944:Organoplatinum Compounds; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; D014688:Venoms; D000077150:Oxaliplatin; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D053148:Caspase 3