The mechanism of lovastatin in suppressing the proliferation of esophageal squamous cell carcinoma based on proteomics

J Gene Med. 2024 Aug;26(8):e3722. doi: 10.1002/jgm.3722.

Abstract

Background: Lovastatin, a type of statin usually considered as a lipid-lowering drug that lowers blood cholesterol and low-density lipoprotein cholesterol levels, has been rediscovered to have anticancer activity. Fewer studies exist regarding the effect of lovastatin on esophageal squamous cell carcinoma (ESCC).

Methods: Here, we report that lovastatin shows anticancer effect on ESCC By affecting the mitochondrial autophagy pathway. Moreover, based on proteomics and computer molecular simulations found that RAB38 and RAB27A may be a target of lovastatin.

Results: We observed that autophagy of mitochondria is inhibited by lovastatin, affecting esophageal squamous cell proliferation. There is a possible link between the expression of RAB38, RAB27A and immune cell invasion in esophageal cancer.

Conclusions: These results demonstrate the huge potential of lovastatin as an RAB38, RAB27A inhibitor in esophageal cancer chemotherapy and chemoprevention.

Keywords: chemotherapy; esophageal squamous cell carcinoma; lovastatin; mitochondrial autophagy; proteomics.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Autophagy* / drug effects
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / metabolism
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / drug therapy
  • Esophageal Squamous Cell Carcinoma* / metabolism
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lovastatin* / pharmacology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Molecular Docking Simulation
  • Proteomics* / methods
  • rab GTP-Binding Proteins / metabolism

Substances

  • Lovastatin
  • rab GTP-Binding Proteins
  • Antineoplastic Agents