Exenatide inhibits the growth of endometrial cancer Ishikawa xenografts in nude mice

Zhang,Yu; Xu,Fen; Liang,Hua; Cai,Mengyin; Wen,Xinqiao; Li,Xiaomao; Weng,Jianping

doi:10.3892/or.2015.4476

Exenatide inhibits the growth of endometrial cancer Ishikawa xenografts in nude mice

Authors:
- Yu Zhang
- Fen Xu
- Hua Liang
- Mengyin Cai
- Xinqiao Wen
- Xiaomao Li
- Jianping Weng
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Affiliations: Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China, Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China, Department of Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, P.R. China
Published online on: December 8, 2015 https://doi.org/10.3892/or.2015.4476
Pages: 1340-1348

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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.

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