Effect of the GLP-1 Analog Exendin-4 and Oxaliplatin on Intrahepatic Cholangiocarcinoma Cell Line and Mouse Model

International Journal of Molecular Sciences

Ben-Dong Chen⁴  Wen-Chao Zhao¹  Qing-An Jia³  Wen-Yan Zhou²  Yang Bu⁴  Zuo-Zheng Wang⁴  Feng Wang⁴  Wu-Jun Wu³ 

[1]Department of Hepatobiliary Surgery, Navy General Hospital, Beijing 100086, China

[2] E-Mail:

[3]Department of ICU, Ningxia Medical University, Yinchuan 750004, Ningxia, China

[4] E-Mail:

[5]Department of Hepatobiliary Surgery, Shannxi Province People’s Hospital, Xi’an 710071, Shannxi, China

[6] E-Mails:

[7]Department of Hepatobiliary Surgery, Ningxia Medical University, Yinchuan 750004, Ningxia, China

[8] E-Mails:

关键词: intrahepatic cholangiocarcinoma;    GLP-1;    exendin-4;    mice;    PCNA;   

DOI  :  10.3390/ijms141224293

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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