Abstract:Objective: To investigate the effects of the heparanase (HPSE) inhibitor OGT2115 on pain behaviors and tumor progression in a mouse model of bone cancer pain (BCP). Methods: A BCP mouse model was established by inoculating Lewis lung carcinoma (LLC) cells into the femur. Animals were randomly divided into a sham-operated group (Sham), a model group (BCP), and an OGT2115 intervention group (BCP+OGT2115). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of the affected hind paw were dynamically monitored. Tumor-induced bone destruction and soft tissue swelling were assessed via X-ray imaging and the ratio of affected-to-contralateral leg circumference. For the in vitro experiments, LLC cells were divided into three groups: LLC, LLC+Veh, and LLC+OGT2115. The effects of OGT2115 on LLC cell migration and proliferation were evaluated using Transwell migration assays and EdU proliferation assays, respectively. Results: Compared with the Sham group, mice in the BCP group developed progressive mechanical and thermal hypersensitivity, accompanied by significant bone destruction and leg swelling. OGT2115 intervention significantly increased the pain threshold, alleviated pain hypersensitivity, and reduced the leg circumference ratio in BCP mice, indicating inhibition of tumor growth. In vitro experiments confirmed that OGT2115 directly inhibited the migration and proliferation of LLC cells. Conclusion: The HPSE inhibitor OGT2115 effectively alleviates pain hypersensitivity in a BCP model. Its analgesic mechanism may be related to the inhibition of tumor cell proliferation and migration within the bone, thereby reducing tumor burden and associated damage to bone tissue and nerves.
