Effect of survivin downregulation by simvastatin on the growth and invasion of salivary adenoid cystic carcinoma

Mol Med Rep. 2018 Aug;18(2):1939-1946. doi: 10.3892/mmr.2018.9204. Epub 2018 Jun 22.

Abstract

Simvastatin, an inhibitor of 3‑hydroxy‑3-methylglutaryl‑coenzyme A reductase, is been used in the clinic due to its pleiotropic effects, such as breast cancer, prostate cancer, pancreatic cancer. Simvastatin has recently been demonstrated to serve a potential role in the prophylaxis and therapeutics of a number of human cancers. The majority of reports concerning simvastatin treatment in the majority of human cancers have demonstrated that survivin is significantly decreased as a result and has been implicated in tumorigenesis. However, only a limited number of studies have investigated the use of simvastatin for the treatment of salivary gland adenoid cystic carcinoma (SACC). Therefore, this agent is a candidate for further investigation. The aim of the present study was to investigate the effects of simvastatin on the proliferation, invasion and apoptosis of the human salivary adenoid cystic carcinoma cell line, SACC‑83, as well as survivin expression in the cells. The Cell Counting kit‑8 assay results revealed that simvastatin inhibited the proliferation of SACC‑83 cells in a dose‑dependent (10 to 50 µM) and time‑dependent (24 to 48 h) manner when compared with the untreated cells. Flow cytometry analysis indicated that simvastatin increased the percentage of cells in early and late apoptosis. Invasion assays revealed that simvastatin treatment inhibited the invasiveness of SACC‑83 cells in a dose‑dependent manner. In addition, simvastatin downregulated survivin expression in SACC‑83 cells. In conclusion, simvastatin significantly inhibited the proliferation and invasion of SACC‑83 cells, induced apoptosis, and reduced the expression of survivin, which suggests that simvastatin may be a novel target for SACC therapy.

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Adenoid Cystic / drug therapy
  • Carcinoma, Adenoid Cystic / metabolism*
  • Carcinoma, Adenoid Cystic / pathology
  • Cell Line, Tumor
  • Down-Regulation / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis*
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis*
  • Salivary Gland Neoplasms / drug therapy
  • Salivary Gland Neoplasms / metabolism*
  • Salivary Gland Neoplasms / pathology
  • Simvastatin / pharmacology*
  • Survivin

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • Survivin
  • Simvastatin