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 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.