1, 25-dihydroxy vitamin D3 inhibits Ras-MEK-ERK pathway and regulates proliferation and apoptosis of papillary thyroid carcinoma

Abstract Objective To explore the effects of 1, 25-dihydroxy vitamin D3 [1, 25-(OH)2D3] on proliferation and apoptosis of papillary thyroid carcinoma, and to investigate its possible mechanism. Materials and Methods The papillary thyroid carcinoma cell line TPC-1 was cultured and the cells were divided into control group, the 1, 25-(OH)2D3 group and 1, 25-(OH)2D3+ML-098 (Ras agonist) group. Cell proliferation was observed by MTT. The colony-formation viability of cell was detected by plate cloning assay. Cell migration was observed by scratch assay. The apoptosis was detected by Flow cytometry. The expression of Ki67, Caspase-3 and the activity of Ras-MEK-ERK pathway were detected by Western-blot. Results Compared with the Control group, the proliferation, colony formation and migration ability of cells in the drug group were significantly decreased. The number of apoptotic cells was significantly increased, the expression of Ki67 protein was decreased, and the expression of Caspase-3 protein was up-regulated. The phosphorylation levels of Ras, p-ERK1/2 and p-MEK were decreased. Compared with the drug group, the cloning and migration biological activity of cells in 1, 25-(OH)2D3+ML-098 group was significantly enhanced (p Conclusion 1, 25-(OH)2D3 can inhibit the activity and promote apoptosis of papillary thyroid carcinoma cell line TPC-1, and its mechanism may be related to the inhibition of Ras-MEK-ERK pathway activity, thus affecting the proliferation and the expression of apoptosis-related proteins.