Exploring the anti-papillary thyroid carcinoma effect of sulforaphane based on TLR4/MAPK/NF-κB signaling pathway
Objective To investigate the effect and mechanism of sulforaphane on papillary thyroid carcinoma xenografts in nude mice.Methods A nude mouse model of human papillary thyroid carcinoma xenograft was constructed by subcutaneous injection of TPC-1 cells.The model mice were randomly divided into the model group,the low-dose group of sulforaphane,and the high-dose group of sulforaphane,with 10 mice in each group.The low-dose group and high-dose group of sulforaphane were orally administered with 5 mg/kg and 20 mg/kg sulforaphane,respectively.The model group was orally administered with an equal amount of saline once a day for 25 consecutive days.Tumor growth was measured every 5 d.The mass of the tumor was weighed and the tumor inhibition rate was calculated.TUNNEL method was used to observe the apoptosis of tumor tissue cells.ELISA is used to detect the levels of serum inflammatory factors and oxidative stress indicators.Flow cytometry was used to detect the ratio of CD4+/CD8+lymphocyte subsets in the blood.Western blot was used to detect the expression of TLR4,P38,and p-NF-κB proteins in tumor tissues.Results Compared with the model group,the tumor growth rate was significantly inhibited,the tumor mass was reduced,the tumor inhibition rate was increased,and the positive rate of tumor cell apoptosis was increased(P<0.01).The levels of serum TNF-α,IL-1β and IL-6 were lowered,the levels of serum GSH-Px and SOD were increased,and serum MDA levels were decreased(P<0.01).The ratio of CD4+/CD8+lymphocyte subsets in blood was enhanced,and the relative expression of TLR4,P38 and p-NF-κB protein in tumor tissue was decreasedin a dose-dependent manner.Conclusion Sulforaphane has anti-papillary thyroid carcinoma effects,and its mechanism is mainly related to the regulation of TLR4/MAPK/NF-κB pathway,anti-inflammatory and oxidative stress,and immune regulation.