Ibrutinib Inhibits Tumor Progression, Alleviates Pain, and Protects the Tibia in a Bone Metastasis Model of Lung Cancer

Background/Aim: Lung cancer bone metastasis significantly reduces the quality of life of advanced-stage patients, leading to cancer-related pain and pathological fractures. Currently, there is a lack of drugs simultaneously inhibiting the growth of metastatic lesions and reducing pain. Ibrutinib, a selective inhibitor of EGFR-mutated non-small cell lung cancer, has been shown to inhibit the proliferation and migration of lung cancer cells. This study aimed to investigate the effects of ibrutinib on tumor progression, pain, and bone protection.

Materials and Methods: Cell viability and migration of the murine Lewis lung carcinoma (LLC, FH0325) and human NSCLC (NCI-H1975, FH0086) cell lines were assessed using CCK-8, wound healing, and transwell assays after treatment with ibrutinib. Behavior tests, mechanical allodynia, flinches and pain scoring, micro-computed tomography and histological analysis were evaluated on the tumor-bearing C57BL/6 mice.

Results: CCK-8, wound healing, and transwell assays demonstrated that ibrutinib significantly suppressed the proliferation and migration of lung cancer cell lines. The efficacy of ibrutinib treatment was evaluated in a mouse model of lung cancer bone metastasis. Behavioral analysis validated the reduction in mechanical and spontaneous pain and the delay in the loss of motor function. Micro-CT revealed greater bone volume and density and less bone trabecular separation. Moreover, TRAP staining indicated a decrease in osteoclast numbers following ibrutinib treatment. Histopathological examination revealed fewer lung metastatic lesions, while TUNEL staining indicated more severe tumor cell apoptosis induced by ibrutinib.

Conclusion: Ibrutinib effectively inhibited the proliferation and migration of lung cancer cells, and in a lung cancer bone metastasis model, this drug inhibited tumor growth, alleviated pain, and protected the tibial bone.