Abstract
Astragalus polysaccharides (APS), which is widely used as a remedy to promote immunity of breast cancer patients, can enhance immune responses and exert anti-tumor effects. In this study, we investigated the effects and mechanisms of APS on macrophage RAW 264.7 and EAC tumor-bearing mice. Griess reaction and ELISA assays revealed that the concentrations of nitric oxide, TNF-α, IL-1β and IL-6 were increased by APS. However, this effect was diminished in the presence of TAK-242 (TLR4 inhibitor) or ST-2825(MyD88 inhibitor). In C57BL/10J (TLR4+/+wild-type) and C57BL/6J (MyD88+/+wild-type) tumor-bearing mice, the tumor apoptosis rate, immune organ indexes and the levels of TNF-α, IL-1β and IL-6 in blood increased and the tumor weight decreased by oral administration of APS for 25 days. APS had no obvious effects on IL-12p70. However, these effects were not significant in C57BL/10ScNJ (TLR4-deficient) and C57BL/B6.129P2(SJL)-Myd88m1.1Defr/J (MyD88-deficient) tumor-bearing mice. qRT-PCR and Western blot indicated that APS stimulated the key nodes in the TLR4-MyD88 dependent signaling pathway, including TLR4, MyD88, TRAF-6, NF-κB and AP-1, both in vitro and in vivo. However, TRAM was an exception. Moreover, TRAF-6 and NF-κB were not triggered by APS in gene-deficient tumor-bearing mice. Therefore, APS may modulate immunity of host organism through activation of TLR4-mediated MyD88-dependent signaling pathway.
Highlights
Breast cancer is the most common cancer among women and the leading cause of cancer-related death worldwide[1]
The results suggest that Astragalus polysaccharides (APS) can stimulate RAW 264.7 macrophages to secrete nitric oxide (NO), IL-1β, IL-6 and TNF-αin vitro
NO, synthesized by macrophage-induced nitric oxide synthase, has been identified as a major effect molecule involved in many biological processes[31], including pathogen elimination[32] and destruction of tumor cells by activated macrophages[33]
Summary
Breast cancer is the most common cancer among women and the leading cause of cancer-related death worldwide[1]. Astragalus polysaccharides (APS), the main active extract from Astragalus membranaceus, has been well recognized as an anti-tumor immunomodulator and widely applied in clinic[9,10]. It has a molecular weight of 3.6 × 104 Da and has a variety of bio-activities[11,12,13,14,15]. Whether the immunomodulatory and anti-tumor effects of APS is mediated through TLR4 signaling pathway is still unclear. This study was designed to investigate the role and mechanism of TLR4 signaling pathway in APS-induced immunoregulation and tumor inhibition
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
