摘要
OBJECTIVE:To study the effect and underlying mechanisms of Chinese medicine Yanghe decoction(阳和汤)on pain relief in a rat model of bone metastasis of breast cancer induced by michigan cancer foundation-7(MCF-7).METHODS:Bone pain was induced in the tibia of rats injected with MCF-7 cells.The Chinese herbal remedy was used to decoct Yanghe decoction for the treatment of bone pain rats.The behavior study was carried out to evaluate the paw mechanical withdraw threshold and thermal withdraw latency.Liquid chromatography-mass spectrometry,Western blotting,quantitative real-time polymerase chain reaction,enzyme-linked immunosorbent assay(ELISA),immunohistochemical(IHC)staining were performed for analysis.RESULTS:Yanghe decoction could improve the defensive behavior similar to the transient receptor potential ankyrin 1(TRPA1)inhibitor.In morphology study,Yanghe decoction could attenuate the cellular growth as well as inflammatory infiltration in the metastasis group.Furthermore,Yanghe decoction downregulated the TRPA1 expression on the dorsal root ganglion from the metastatic rats at both transcriptional and protein level.Yanghe decoction alleviated the inflammation in metastatic tissues by hematoxylin-eosin and IHC analysis,and Yanghe decoction also reduced the inflammatory cytokines production in the serum including tumor necrosis factor-αand interleukin-6,interleukin-1 beta by ELISA.As the cytochromec oxidase subunit II/prostaglandin E2(PGE2)is required for cancer development,Yanghe decoction reduced the expression of PGE2 in the tissue and serum.CONCLUSION:Taken together,Yanghe decoction protected the rats from breast cancer bone metastasis through TRPA1 signaling mediated neuropathic pain and additional immune modulation in tumor microenvironment.
基金
Supported by China Postdoctoral Science Foundation Grant:Pathogenesis of“Impassability Leads to Pain”about Bone Metastasis based on Proinflammatory Cytokines Activate TRPA1(No.2018M632971)
Hunan Natural Science Foundation of China:Study on the Effect and Mechanism of Yanghe Decoction Regulating cxcl12/cxcr4 Biological Axis against Bone Metastasis of Breast Cancer in Yang Deficiency Syndrome(No.2020JJ8088)
General Project of Natural Science Foundation of Hunan Province:Study on the Mechanism of Bone Loss in Breast Cancer Bone Metastasis by Warm Yang Method from the Pathway of TNF-α/NF-κB/Autophagy(No.2021JJ30418)
Social Development Project of Key R&D Science and Technology Program of Hainan Province:Clinical Efficiency of Liushen Pill in Treatment of Bone Cancer Pain and Study on the Analgesic Mechanism of Bone Cancer Pain of Rat Model(No.ZDYF2021SHFZ225)。
