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Combination of gemcitabine and erlotinib inhibits recurrent pancreatic cancer growth in mice via the JAK-STAT pathway

  • Authors:
    • Liwen Chen
    • Ding'an Zhou
    • Zhehao Liu
    • Xinhao Huang
    • Qianfan Liu
    • Yiping Kang
    • Zili Chen
    • Yuntao Guo
    • Haitao Zhu
    • Chengyi Sun

  • View Affiliations

  • Published online on: January 8, 2018     https://doi.org/10.3892/or.2018.6198
  • Pages: 1081-1089

  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Compared to single gemcitabine treatment, the combination of gemcitabine and erlotinib has shown effective response in patients with locally advanced or metastatic pancreatic cancer. However, the combination therapy has not proven effective in patients with pancreatic cancer after R0 or R1 resection. In the present study, a nude mice model of orthotopic xenotransplantation after tumor resection was established using pancreatic cancer cell lines, BxPC-3 and PANC‑1. Mice were divided in four groups (each with n=12) and were treated as follows: the control group received a placebo via intraperitoneal injection (i.p.), while the other three groups were treated with gemcitabine (50 mg/kg i.p., twice a week), erlotinib (50 mg/kg oral gavage, once every three days), and combined treatment of gemcitabine and erlotinib, respectively. The treatment lasted for 21 days, after which all mice were sacrificed and tumors were examined ex vivo. We determined that the combination of gemcitabine and erlotinib inhibited recurrent tumor growth and induced apoptosis in vivo by downregulating phosphorylation levels of JAKs and STATs, which in turn downregulated the downstream proteins HIF‑1α and cyclin D1, and upregulated caspase‑9 and caspase‑3 expression. To sum up, the combination of gemcitabine with erlotinib was effective in treating patients with pancreatic cancer after R0 or R1 resection.
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March-2018
Volume 39 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Chen L, Zhou D, Liu Z, Huang X, Liu Q, Kang Y, Chen Z, Guo Y, Zhu H, Sun C, Sun C, et al: Combination of gemcitabine and erlotinib inhibits recurrent pancreatic cancer growth in mice via the JAK-STAT pathway. Oncol Rep 39: 1081-1089, 2018
APA
Chen, L., Zhou, D., Liu, Z., Huang, X., Liu, Q., Kang, Y. ... Sun, C. (2018). Combination of gemcitabine and erlotinib inhibits recurrent pancreatic cancer growth in mice via the JAK-STAT pathway. Oncology Reports, 39, 1081-1089. https://doi.org/10.3892/or.2018.6198
MLA
Chen, L., Zhou, D., Liu, Z., Huang, X., Liu, Q., Kang, Y., Chen, Z., Guo, Y., Zhu, H., Sun, C."Combination of gemcitabine and erlotinib inhibits recurrent pancreatic cancer growth in mice via the JAK-STAT pathway". Oncology Reports 39.3 (2018): 1081-1089.
Chicago
Chen, L., Zhou, D., Liu, Z., Huang, X., Liu, Q., Kang, Y., Chen, Z., Guo, Y., Zhu, H., Sun, C."Combination of gemcitabine and erlotinib inhibits recurrent pancreatic cancer growth in mice via the JAK-STAT pathway". Oncology Reports 39, no. 3 (2018): 1081-1089. https://doi.org/10.3892/or.2018.6198