Exogenous Hydrogen Sulfide Regulates the Growth of Human Thyroid Carcinoma Cells.

Hydrogen sulfide (H(2)S) is involved in the development and progression of many types of cancer. However, the effect and mechanism of H(2)S on the growth of human thyroid carcinoma cells remain unknown. In the present study, we found that the proliferation, viability, migration, and invasion of human thyroid carcinoma cells were enhanced by 25-50 μM NaHS (an H(2)S donor) and inhibited by 200 μM NaHS. However, H(2)S showed no obvious effects on the proliferation, viability, and migration of human normal thyroid cells. Administration of 50 μM NaHS increased the expression levels of CBS, SQR, and TST, while 200 μM NaHS showed reverse effects in human thyroid carcinoma cells. After treatment with 25-50 μM NaHS, the ROS levels were decreased and the protein levels of p-PI3K, p-AKT, p-mTOR, H-RAS, p-RAF, p-MEK1/2, and p-ERK1/2 were increased, whereas 200 μM NaHS exerted opposite effects in human thyroid carcinoma cells. Furthermore, 1.4-2.8 mg/kg/day NaHS promoted the tumor growth and blood vessel formation in human thyroid carcinoma xenograft tumors, while 11.2 mg/kg/day NaHS inhibited the tumor growth and angiogenesis. In conclusion, our results demonstrate that exogenous H(2)S regulates the growth of human thyroid carcinoma cells through ROS/PI3K/Akt/mTOR and RAS/RAF/MEK/ERK signaling pathways. Novel H(2)S-releasing donors/drugs can be designed and applied for the treatment of thyroid cancer.