RESUMO
Pancreatic cancer is accompanied by poor prognosis and accounts for a significant number of deaths every year. Since Psoralea corylifolia L. (PCL) possesses a broad spectrum of bioactivities, it is commonly used in traditional Chinese medicine. The study explored potential antitumor agents of PCL and underlying mechanisms in vitro and vivo. Based on network pharmacology, bioinformatics, and molecular docking, we considered isobavachalcone (IBC) as a valuable compound. The activity and potential mechanisms of IBC were investigated by RT-qPCR, immunohistochemistry, immunofluorescence, and flow cytometry. It was confirmed that IBC could inhibit Panc 02 cell proliferation and induce apoptosis via increasing the production of reactive oxygen species. IBC could attenuate the weight of solid tumors, increase CD8+ T cells, and reduce M2 macrophages in the tumor tissue and spleen. Another promising finding was that IBC alleviated the proportion of myeloid-derived suppressor cells (MDSCs) in the tumor tissue but had no change in the spleen. The study of pharmacological effects of IBC was carried out and suggested IBC restrained M2-like polarization of RAW 264.7 cells by inhibiting the expression of ARG1 and MRC1 and suppressed the expression of ARG1 and TGF-ß in bone marrow-derived MDSC. In summary, this research screened IBC as an antineoplastic agent, which could attenuate the growth of pancreatic cancer via activating the immune activity and inducing cell apoptosis. It might be a reference for the antitumor ability of IBC and the treatment of the tumor microenvironment in pancreatic cancer.
RESUMO
Primary contents of dietary fat are three or four types of fatty acids, namely saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n6-polyunsaturated fatty acid (n6PUFA) and, to less extent, n3-polyunsaturated fatty acid (n3PUFA). Previous studies suggest that increased SFA, MUFA, and n6PUFA in high fat diets (HFDs) stimulate the origination, growth, and liver metastasis of pancreatic cancer cells, whereas increased n3PUFA has the opposite effects. It is unclear whether the fatty acid-induced effects are based on changed fatty-acid composition of involved cells. Here, we investigated whether increased SFA, MUFA, n6PUFA, and n3PUFA in different HFDs determine the FA profiles of pancreatic cancer cells and their carrier's plasma, pancreas, and liver. We transplanted MiaPaCa2 human pancreatic cancer cells in athymic mice and fed them normal diet or four HFDs enriched with SFA, MUFA, n6PUFA, and n3PUFA, respectively. After 7 weeks, fatty acids were profiled in tumor, plasma, pancreas, and liver, using gas chromatography. When tumor carriers were fed four HFDs, the fatty acids that were increased dietarily were also increased in the plasma. When tumor carriers were fed MUFA-, n6PUFA-, and n3PUFA-enriched HFDs, the dietarily increased fatty acids were also increased in tumor, pancreas, and liver. When tumor-carriers were fed the SFA-enriched HFD featuring lauric and myristic acids (C12:0 and C14:0), tumor, pancreas, and liver showed an increase not in the same SFAs but palmitic acid (C16:0) and/or stearic acid (C18:0). In conclusion, predominant fatty acids in HFDs determine the fatty-acid profiles of pancreatic cancer cells and their murine carriers.
Assuntos
Gorduras na Dieta/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Fígado/metabolismo , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Animais , Linhagem Celular Tumoral , Dieta Hiperlipídica , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Ácidos Graxos Monoinsaturados/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Humanos , Camundongos , Camundongos Nus , Transplante de NeoplasiasRESUMO
Pancreatic cancer is a digestive tract malignancy that poses a serious threat to human health. Compounds derived from traditional Chinese medicines have been an important source of anticancer drugs and adjuvant agents to regulate the tumor immune microenvironment in patients with pancreatic cancer. In this study, icariin was purified from Herba Epimedii using macropores, and its bioactivity against pancreatic cancer was also investigated. We found that icariin has direct inhibitory and immunomodulatory effects on tumor cells. In vitro experiments showed that icariin can inhibit the migration and proliferation of Panc02 pancreatic cancer cells and induce apoptosis. Our in vivo experiments show that icariin inhibits the development of mouse pancreatic cancer by inhibiting tumor-infiltrating M2 macrophages and polymorphonuclear myeloid-derived suppressor cells (MDSCs) (PMN-MDSCs). In addition, icariin inhibits the polarization of RAW 264.7 cells into M2 macrophages by inhibiting the expression of ARG1 and MRC1 and downregulating the IL4-STAT6 signaling pathway. In conclusion, the inhibitory effect of icariin on pancreatic cancer can not only directly affect tumor cells but also inhibit tumor development by regulating the tumor immune microenvironment.