Matrine inhibits TPC-1 human thyroid cancer cells via the miR-21/PTEN/Akt pathway.

Abstract

Papillary thyroid cancer (PTC) is the primary type of thyroid cancer and the most widespread endocrine malignancy. Matrine is a traditional Chinese medicine and has been demonstrated as a promising alternative drug for the treatment of TPC-1 human PTC. In the present study, the therapeutic effects and the underlying molecular mechanisms of matrine on TPC-1 cells were investigated. Treatment with matrine at the concentrations of 1, 2, 5, 10 and 20 mg/ml inhibited TPC-1 cell proliferation by up to 95.8% (for 20 mg/ml matrine). Flow cytometry indicated that treatment with 10 mg/ml matrine induced up to 61.8% apoptosis of the TPC-1 cells and the cell cycle was arrested at the G0/G1 phase following treatment with matrine (2, 5 and 10 mg/ml) for 48 h. Quantitative polymerase chain reaction indicated that the expression of microRNA (miR)-21 was downregulated and phosphatase and tensin homolog (PTEN) mRNA levels increased up to 1.66-fold following treatment with matrine, and RAC-α serine/threonine-protein kinase (Akt) mRNA levels were downregulated 0.34-fold following treatment with 5 mg/ml matrine, compared with the normal control group. Western blot analysis indicated that matrine at 2 and 5 mg/ml increased levels of the miR-21 target PTEN and decreased the levels of phosphorylated (p)Akt. Furthermore, miR-21 mimic transfection decreased the expression levels of PTEN and increased the levels of pAkt. These results suggested that the miR-21/PTEN/Akt pathway may be one of the mechanisms by which matrine induces apoptosis and cell cycle arrest in TPC-1 thyroid cancer cells. Matrine is an alternative potential drug for the treatment of thyroid cancer.