Abstract
Tumor associated macrophage (TAM) is an important component in tumor microenvironment. Generally, TAM exhibits the function of M2-like macrophage, which is closely related to angiogenesis and tumor progression. Dioscin, a natural steroidal saponin, has shown its powerful anti-tumor activity recently. However, the mechanism of dioscin involved in immune-regulation is still obscure. Our study aimed to find the potentional anti-tumor role of dioscin in macrophages polarization regulation in lung cancer. Flow cytometry was used to analyze the percentage of M1 macrophages(CD86+F4/80+ or NOS2+F4/80+) and M2 macrophages(CD209+F4/80+ or CD206+F4/80+) with dioscin treatment in vivo and in vitro. Real-time quantitative PCR was used to detect the expression of Arg-1, CD206 and NOS2, IL-6 mRNA. The level of IL10 and IL-12 secreted by macrophages was also analyzed using flow cytometry. Phagocytosis was determined by the amount of fluorescence-labeled latex beads internalized by BMDMs with microscopy and Flow cytometry. JAK-STAT and MAPK signaling pathways were detected by Western-Blot method. We observed dioscin induced macrophages M2-to-M1 phenotype transition in vitro and inhibited IL-10 secretion. Meanwhile, the phagocytosis of macrophages was enhanced. In subcutaneous lung tumor models, dioscin inhibited the augmentation of M2 macrophage populations. Furthermore, dioscin down-regulated STAT3 and JNK signaling pathways in macrophages in vitro. Additionally, condition mediums from dioscin-pretreated macrophages inhibited the migration of 3LL cells and the tube-formation capacity of HUVEC cells. Dioscin may act as a new anti-tumor agent by inhibiting TAMs via JNK and STAT3 pathways in lung cancer.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call