<p>Resatorvid Relieves Breast Cancer Complicated with Depression by Inactivating Hippocampal Microglia Through TLR4/NF-κB/NLRP3 Signaling Pathway</p>

Abstract

Background Breast cancer is one of the most common cancer with high risk in females all over the world. It is usually complicated with depression, which can further accelerate the development and progression of breast tumors. We aim to identify a new drug and identify its functional mechanism in the regulation of hippocampal microglia (MG) in breast cancer complicated with depression (BCCD). Methods The activation model of MG was established by treatments from corticosterone (CORT) or lipopolysaccharides (LPS). The inhibitory effects of resatorvid on MG were investigated by CCK-8, ROS, immunofluorescence, TUNEL, scratch test, ELISA, RT-qPCR and Western blot. BCCD animal model was established using 4T1 inflammatory breast cancer cells and CORT treatment in vitro. Open field experiment (OFE), tail suspension test (TST), ELISA, RT-qPCR and Western blot experiments were utilized to examine the effects of resatorvid on the animal model in vivo. Results The cell viability and migration ability of the BCCD model group were suppressed. The expressions of inflammatory factors, ROS, and the apoptotic rate of the BCCD model group were up-regulated, in contrast to the control group. The expressions related to the TLR4/NF-κB/NLRP3 signaling in the BCCD model group were also elevated. Resatorvid reversed the above changes, which showed good therapeutic effects in depression-related behavioral changes, tumor treatment, and blood–brain barrier function. Conclusion In summary, resatorvid inhibited the activation of hippocampal MG in BCCD by regulating TLR4/NF-κB/NLRP3 signaling pathway.

Quercetin Alleviates the Progression of Breast Cancer-Related Depression via Inhibiting the Pyroptosis and Promoting the Immune Response

“…In addition, mice in the control, depression, BCRD, and breast cancer group were administered with the same amount of distilled water. After 3 weeks of treatment, each group of mice was analyzed according to multiple indicators [ 16 ].…”

“…Then, cells were centrifuged, and the supernatants were collected. The cell supernatants and 200 μM CORT were added to primary neurons for 6 h [16]. placed in the condition of SPF.…”

A review on traditional Chinese medicine natural products and acupuncture intervention for Alzheimer’s disease based on the neuroinflammatory

“…With the increase of NF-κB transcription, NLRP3 [ 78 ] inflammasome is activated as a multiprotein complex in the cytoplasm. After assembly, the proinflammatory caspase-1 precursor protein is activated into aspase-1, and the inflammatory cytokines IL-1β, IL-6, IL-18 [ 79 ] are secreted to induce the immune response of the body. The establishment of a chronic inflammatory environment in the brain can lead to neuronal injury and eventually lead to inflammatory cascade, which further aggravates the course of AD.…”

Pinocembrin ameliorates depressive-like behaviors by regulating P2X7/TRL4 receptors expression in mouse hippocampus

“…It could affect the immune response by activating downstream signaling pathways and mediating innate immune responses. NLRP3 inflammasomes acted as vital signaling molecule downstream of TLR4, which promotes the maturation of inflammatory cytokines (Luo et al , 2020). Although P2X7/TLR4 receptor-dependent NLRP3 inflammasome activation in morphine tolerance has been demonstrated (Wang et al , 2020), the mechanism of the P2X7/TLR4 pathway in depression is still a question.…”