Effects of Denosumab on pain threshold,coagulation function and TAK1/JNK/c-Jun pathway activity in bone cancer pain rats
DUAN Deng-ke
BAI Zhi-long
WEN Zhen-tao
WANG Yan
SUN Bang-jian
Abstract：Objective To study the effects of Denosumab on pain threshold,coagulation function and TAK1/JNK/c-Jun signaling pathway in bone cancer pain rats.Methods SD rats were randomly divided into four groups,sham operation group,model group,Denosumab group,and JNK inhibitor group.Except for the sham surgery group,rats in the other groups were injected with Walker 256 breast cancer cell suspension into the right tibia to establish a bone cancer pain model.After modeling,mechanical withdrawal threshold and thermal withdrawal latency were measured before and after drug administration.Conventional coagulation function indicators were detected,and X-ray images were used to assess bone destruction.Enzyme-linked immunosorbent assay(ELISA)was used to measure spinal cord-related cyto-kine levels,and Western blot was performed to detect the expression of proteins related to the TAK1/JNK/c-Jun signa-ling pathway.Results Compared with the sham surgery group,the model group showed a significant decrease in mechan-ical withdrawal threshold,thermal withdrawal latency,and coagulation function,with obvious bone destruction.The levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),interleukin-1 beta(IL-1 β),and monocyte che-moattractant protein(CCL2)were significantly increased,while the expression of p-TAK1,p-JNK,and p-c-Jun proteins in the spinal cord was significantly upregulated(P＜0.05).Compared with the model group,rats in the Deno-sumab and JNK inhibitor groups showed significant increases in mechanical withdrawal threshold and thermal withdrawal latency,improved coagulation function,and significant repair of bone destruction.The levels of TNF-α,IL-6,IL-1β,and CCL2 were significantly reduced,while the expression of p-TAK1,p-JNK,and p-c-Jun proteins in the spinal cord was significantly downregulated(P＜0.05).Conclusion Denosumab can alleviate bone cancer pain in rats,inhibit coagulation dysfunction,and reduce inflammation.Its mechanism may be related to the activation of the TAK1/JNK/c-Jun signaling pathway proteins.
Keywords：DenosumabBone cancer painCoagulation functionTAK1/JNK/c-Jun signaling pathway
Publication Date：2025-04-15
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 519-524 )