title: Exenatide inhibits the growth of endometrial cancer Ishikawa xenografts in nude mice.
abstract: Studies have showed that diabetes is one of the high risk factors of endometrial cancer; however, no reports describe the anti- or pro-cancer effect of a new kind of anti-diabetes drug, glucagon-like peptide-1 receptor agonist exenatide (exendin-4), on endometrial cancer. To investigate whether exenatide promotes or inhibits the growth of endometrial cancer, we used the subcutaneous human endometrial cancer cell Ishikawa xenografts in nude mouse model, and divided them into control group and exenatide-treated group. The tumor growth rate in exenatide group was slower than that in control group, and the apoptosis rate of exenatide group was higher than that in control group. In vitro, exendin-4 also attenuated Ishikawa cell viability and clone formation rate, but promoted cell apoptosis. There was an increase of phosphorylated-AMPK protein, a decrease of phosphorylated-mTOR protein both in vivo and in vitro after exenatide or exendin-4 treatment. Moreover, when treated with exendin-4 plus AICAR, an AMPK activator, cell apoptosis increased with higher ratio of phosphorylayed-AMPK/AMPK, lower ratio of phosphorylated-mTOR/mTOR and higher expression of cleaved caspase-3 than those in exendin-4 alone group, and the results were the opposite when treated with exendin-4 plus compound C, an AMPK inhibitor. Our results suggest that exenatide could attenuate the growth of endometrial cancer Ishikawa xenografts in nude mice, and AMPK may be the target of the mechanism.
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Mengyin
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Xinqiao
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Xiaomao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Weng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077270:Exenatide; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D010455:Peptides / Q000008:administration & dosage*; D010766:Phosphorylation; D012265:Ribonucleotides / Q000008:administration & dosage; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D014688:Venoms / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D010455:Peptides; D012265:Ribonucleotides; D014688:Venoms; D000620:Aminoimidazole Carboxamide; D000077270:Exenatide; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide