Effect of simvastatin and microRNA-21 inhibitor on metastasis and progression of human salivary adenoid cystic carcinoma

Biomed Pharmacother. 2018 Sep:105:1054-1061. doi: 10.1016/j.biopha.2018.05.157. Epub 2018 Jun 19.

Abstract

Salivary adenoid cystic carcinoma (SACC) is a common malignancy of the salivary glands. Epithelial-mesenchymal transition (EMT) and P53 signaling pathway are associated with SACC metastasis and progression. Although simvastatin (SIM) is effective against the growth of many cancer types, its side effects limit its use. microRNA-21 (miR-21) is highly expressed in a variety of tumors and has a role in promoting tumor development. Therefore, the aim of the present study was to evaluate the effect of SIM in combination with miR-21 inhibitor (miR-21i) against lung metastatic SACC cells (SACC-LM). Our results showed that miR-21i was effective in reducing the resistance of SACC-LM to SIM, resulting in SACC-LM acquisition of epithelial traits, cell migration and invasion reduction, growth inhibition and induction of apoptosis. The expression of proteins associated to metastasis and tumor progression were regulated by the combined use of SIM and miR-21i. Thus, our findings demonstrated that such combination was effective in inhibiting SACC-LM progression, suggesting that multi-target therapy against SACC might represent a potentially successful approach in clinical treatment.

Keywords: Drug resistance; Metastasis; Progression; Salivary adenoid cystic carcinoma; Simvastatin; miR-21.

MeSH terms

  • Carcinoma, Adenoid Cystic / drug therapy
  • Carcinoma, Adenoid Cystic / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Disease Progression*
  • Dose-Response Relationship, Drug
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / physiology
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / metabolism*
  • Salivary Gland Neoplasms / drug therapy
  • Salivary Gland Neoplasms / metabolism*
  • Simvastatin / pharmacology
  • Simvastatin / therapeutic use*
  • Treatment Outcome

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • Simvastatin