Xiaozheng Zhitong Paste Alleviates Bone Cancer Pain by Regulating PD-1/PD-L1-induced Osteoclast Formation
10.13422/j.cnki.syfjx.20252136
- VernacularTitle:消癥止痛外用方调控PD-1/PD-L1诱导的破骨细胞生成减轻骨癌痛
- Author:
Lu SHANG
1
;
Juanxia REN
1
;
Guangda ZHENG
2
;
Linghan MENG
2
;
Lingyun WANG
1
;
Changlin LI
1
;
Dongtao LI
2
;
Yaohua CHEN
3
;
Guiping YANG
3
;
Yanju BAO
2
Author Information
1. Liaoning University of Traditional Chinese Medicine（TCM）， Shenyang 110847， China
2. Guang'anmen Hospital，China Academy of Chinese Medical Sciences，Beijing 100053，China
3. Xining Municipal Hospital of TCM， Xining 810001， China
- Publication Type:Journal Article
- Keywords:
Xiaozheng Zhitong paste （XZP）;
bone cancer pain （BCP）;
osteoclast;
bone damage;
programmed death factor-1 （PD-1）/PD-1 ligand （PD-L1）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(5):72-79
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThis study aims to investigate the action mechanism by which Xiaozheng Zhitong paste （XZP） alleviates bone cancer pain （BCP） by regulating programmed death protein 1 （PD-1）/programmed death-ligand 1 （PD-L1） pathway-induced osteoclast formation. MethodsThirty female C57BL/6 mice were randomly allocated into the following groups （n=6 per group）： normal control group， model group， low‑dose XZP group （31.5 g·kg-1）， high‑dose XZP group （63 g·kg-1）， and PD‑1 inhibitor （Niv） group. A bone cancer pain （BCP） model was established by injecting Lewis lung carcinoma cells. Mice in the normal control and model groups received topical application of a blank paste matrix at the wound site. Mice in the low‑ and high‑dose XZP groups were treated with XZP applied topically twice daily. Mice in the Niv group were topically administered the blank paste matrix and additionally received Niv via tail‑vein injection every two days. All interventions were continued for 21 days. During this period， behavioral tests were performed to assess mechanical， motor， and thermal nociceptive sensitivities. After 21 days， all mice were euthanized， and bone tissue from the operated side was collected for sectioning and preservation. Tartrate‑resistant acid phosphatase （TRAP） staining was used to evaluate osteoclast expression in the lesioned bone tissue. Immunohistochemistry was performed to detect the expression of Runt‑related transcription factor 2 （Runx2） in the lesioned bone tissue. Immunofluorescence was employed to assess the expression of PD‑1 and PD‑L1 in the lesioned bone tissue. ResultsCompared with the normal group， the model group showed significantly decreased limb mechanical withdrawal threshold， spontaneous paw flinching， and thermal withdrawal latency （P<0.01）， increased number of osteoclasts in the lesioned bone tissue （P<0.01）， and reduced expression of Runx2 （P<0.01）. Compared with the model group， the BCP mice in the XZP low-dose group， XZP high-dose group， and Niv group exhibited increased limb mechanical withdrawal threshold， movement scores， and thermal withdrawal latency （P<0.01）. The XZP low-dose group showed no significant changes in osteoclast number or Runx2 expression， while the XZP high-dose group and Niv group demonstrated significantly reduced osteoclast numbers （P<0.01） and significantly increased Runx2 expression （P<0.01）. In the lesioned bone tissue of BCP mice， the XZP low-dose group showed no significant decrease in the percentage of PD-1 expression， but a decrease in the percentage of PD-L1 expression （P<0.05）. In contrast， both the XZP high-dose group and the Niv group exhibited significant reductions in the percentages of PD-1 and PD-L1 expression （P<0.01）. ConclusionXZP alleviates the pain of mice with BCP by blocking the PD-1/PD-L1 pathway to inhibit osteoclastogenesis.
