Osthole inhibits pancreatic cancer progression by directly exerting negative effects on cancer cells and attenuating tumor-infiltrating M2 macrophages

Pancreatic cancer has remained a major cause of cancer-related deaths. A hallmark of pancreatic cancer is extensive stromal reactions, resulting in a unique tumor microenvironment, especially the involvement of macrophages. These tumor-educated cells limit the efficacy of chemotherapy. Therefore, it...

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Veröffentlicht in:Journal of pharmacological sciences 2018-07, Vol.137 (3), p.290-298
Hauptverfasser: Wang, Botao, Zheng, Xin, Liu, Jing, Zhang, Zhen, Qiu, Chongyang, Yang, Lei, Zhang, Lanqiu, Zhang, Qi, Gao, Hongwei, Wang, Ximo
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container_end_page 298
container_issue 3
container_start_page 290
container_title Journal of pharmacological sciences
container_volume 137
creator Wang, Botao
Zheng, Xin
Liu, Jing
Zhang, Zhen
Qiu, Chongyang
Yang, Lei
Zhang, Lanqiu
Zhang, Qi
Gao, Hongwei
Wang, Ximo
description Pancreatic cancer has remained a major cause of cancer-related deaths. A hallmark of pancreatic cancer is extensive stromal reactions, resulting in a unique tumor microenvironment, especially the involvement of macrophages. These tumor-educated cells limit the efficacy of chemotherapy. Therefore, it is necessary to identify an effective treatment strategy. In this study, we aimed to explore the anti-tumor and immunomodulatory effects of osthole on pancreatic cancer. We found that osthole suppressed Panc 02 cell migration and proliferation and induced apoptosis as shown in vitro. Osthole also attenuated the development of pancreatic cancer in mice by inhibiting tumor-infiltrating M2 macrophages in our study. Additionally, osthole inhibited the polarization of primary bone marrow cells into M2 macrophages and inhibited the expression of MRC1, CCL22 and TGF-β in the M2 polarization process in vitro. Detection of the related signaling pathways revealed that osthole exerted immunomodulatory effects on M2 macrophages by down-regulating p-STAT6 and the p-ERK1/2-C/EBP β axis. These results indicated that osthole has effective anti-tumor and immunomodulatory effects on pancreatic cancer.
doi_str_mv 10.1016/j.jphs.2018.07.007
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source DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals
subjects C/EBP β
Osthole
Pancreatic cancer
STAT6
title Osthole inhibits pancreatic cancer progression by directly exerting negative effects on cancer cells and attenuating tumor-infiltrating M2 macrophages
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