Effects of Curcumin on Biological Behavior and NF-κB/TNF-α Pathway in Mice with Metastatic Bone Pain of Breast Cancer Induced by Walker 256 Cells

Abstract

Background. The active ingredient curcumin of traditional Chinese medicine was selected as the research object to investigate the possible mechanism of breast cancer metastatic bone pain in mouse walker 256 cells and the effect of curcumin on the NF-κB/TNF-α pathway in order to provide a new idea for clinical treatment of breast cancer metastatic bone pain. Methods. By establishing an animal model of breast cancer bone metastasis in walker 256 cells, the biological behavior of nude mice was observed on the 8th day after successful modeling. Meanwhile, the low dose group, middle dose group and high dose group of mice were given 15 mg/kg, 25 mg/kg, 50 mg/kg of curcumin solution intraperitoneally in 21 days, and the right cavity bone and spinal cord distended in mice (L4-L6) tissues were used to detect related factors, Immunohistochemical method was used to detect c-fos in spinal cord. Expression levels of RANK, NF-κB and TNF-α were detected by RT-PCR and Western blot. Meanwhile, serum levels of Cox2, il-6, leukotriene and PGE2 were detected. Results. Observing the biological behavior index of nude mice, we found that the mechanical pain and thermal pain threshold decreased (p < 0.05), and the cold pain and spontaneous pain scores increased significantly (p < 0.05). After group study, the expression of c-fos in the cancer pain model group was significantly higher than that in the normal control group (p < 0.05), and with the increase of curcumin dose, the expression of c-fos in the high dose group was significantly lower than that in the solvent model group (p < 0.05). The expression of RANK, NF-κB, TNF-α was higher than that of the normal control group and decreased gradually with the increase of curcumin dose, among which the expression of high dose group was significantly lower than that of solvent group (p < 0.05). RANK, NF-κB, TNF-α protein expression was higher than that of normal control group and gradually decreased with the increase of curcumin dose. The levels of Cox2, IL-6, leukotriene and PGE2 in serum decreased with the increase of curcumin dose, and the high dose group decreased significantly (p < 0.05). Conclusions. On the 8th day after the success of the animal model of breast cancer bone metastasis in Walker 256 cells, abnormal biological behaviors such as heat pain, cold pain sensation and spontaneous hyperalgesia were observed. Further studies have found that the increased expression of rank on osteoclasts induced up-regulated expression of NF-κB and c-fos, induced expression of TNF-α gene, and could induce synthesis and release of leukotriene, PGE2 through direct activation of cyclooxygenase, inflammatory media IL-6 cascade reaction, resulting in pathological pain and hypersensitivity. Traditional Chinese medicine active ingredient curcumin could reduce RANK expression of osteoclast, inhibit cell NF-κB and spinal cord c-fos activity, reduce TNF-α expression, inhibit Cox2 activity, and reduce the synthesis and release of inflammatory factors leukotriene and PGE2, thus exerting its analgesic effect, which provides new ideas and methods for clinical treatment of metastatic bone pain in breast cancer.