Transcriptome sequencing analysis reveals unique and shared antitumor effects of three statins in pancreatic cancer

Oncol Rep. 2020 Dec;44(6):2569-2580. doi: 10.3892/or.2020.7810. Epub 2020 Oct 15.


Statins, a class of commonly prescribed cholesterol‑lowering medications, have been revealed to influence the risk of multiple types of cancer. However, the antitumor effects of statins on pancreatic cancer and their differential efficacy among a variety of statins are not currently well‑defined. The aim of the present study was therefore to identify and compare the genes and related biological pathways that were affected by each individual statin on pancreatic cancer. Two human pancreatic cancer cell lines, MiaPaCa2 and PANC1, were exposed to three statins, lovastatin, fluvastatin and simvastatin. The inhibitory effect of statins on pancreatic cancer cell proliferation was first validated. Next, RNA‑seq analysis was used to determine the gene expression alterations in either low (2 µM) or high (20 µM) statin concentration‑treated cancer cells. Marked differences in gene transcription profiles of both pancreatic cancer cell lines exposed to high concentration statins were observed. Notably, the high concentration statins significantly suppressed core‑gene CCNA2‑associated cell cycle and DNA replication pathways and upregulated genes involved in ribosome and autophagy pathways. However, the low concentration statin‑induced gene expression alterations were only detected in MiaPaCa2 cells. In conclusion, a marked difference in the intra and inter cell‑type performance of pancreatic cancer cells exposed to a variety of statins at low or high concentrations was reported herein, which may provide insights for the potential clinical use of statins in future pancreatic cancer therapeutics.

Keywords: statin; lovastatin; fluvastatin; simvastatin; pancreatic cancer; cell cycle; weighted gene co-expression network analysis.

MeSH terms

  • Autophagy / drug effects
  • Autophagy / genetics
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cyclin A2 / metabolism
  • DNA Replication / drug effects
  • Drug Screening Assays, Antitumor
  • Fluvastatin / pharmacology
  • Fluvastatin / therapeutic use
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Lovastatin / pharmacology
  • Lovastatin / therapeutic use
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • RNA-Seq
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Simvastatin / pharmacology
  • Simvastatin / therapeutic use
  • Transcriptome / drug effects*


  • CCNA2 protein, human
  • Cyclin A2
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Fluvastatin
  • Lovastatin
  • Simvastatin