Ropivacaine Administration Suppressed A549 Lung Adenocarcinoma Cell Proliferation and Migration via ACE2 Upregulation and Inhibition of the Wnt1 Pathway

Int J Mol Sci. 2024 Aug 28;25(17):9334. doi: 10.3390/ijms25179334.

Abstract

Background: Previous studies have suggested that perioperative anesthesia could have direct impacts on cancer cell biology. The present study investigated the effects of ropivacaine administration on lung adenocarcinoma cells.

Methods: Ropivacaine was administered to A549 cells at concentrations of 0.1, 1, and 6 mM for 2 h. Angiotensin-converting enzyme 2 (ACE2) small interfering RNA (siRNA) transfection was performed 6 h prior to ropivacaine administration. Cell proliferation and migration were assessed with cell counting kit 8 (CCK-8) and a wound healing assay at 0 and 24 h after anesthesia exposure. PCR arrays were performed, followed by PCR validation.

Results: Ropivacaine administration inhibited A549 cell proliferation and migration in a concentration-dependent manner, with ACE2 upregulation and HIF1α (hypoxia-inducible factor 1α) downregulation. The anticancer effect of ropivacaine was canceled out via ACE2 siRNA transfection. PCR arrays showed specific gene change patterns in the ropivacaine and respective ACE2-knockdown groups. EGFR (epidermal growth factor receptor), BAX (Bcl-2-associated X protein) and BCL2 (B-cell/CLL lymphoma 2) were suppressed with ropivacaine administration; these effects were reversed via ACE2 siRNA induction.

Conclusion: Ropivacaine administration inhibited A549 cell biology in conjunction with ACE2 upregulation via the inhibition of the Wnt1 (wingless/Integrated 1) pathway.

Keywords: ACE2; HIF1α; PCR array; Wnt1 pathway; ropivacaine.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / metabolism
  • Adenocarcinoma of Lung* / pathology
  • Angiotensin-Converting Enzyme 2* / genetics
  • Angiotensin-Converting Enzyme 2* / metabolism
  • Cell Movement* / drug effects
  • Cell Proliferation* / drug effects
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Ropivacaine* / pharmacology
  • Up-Regulation / drug effects
  • Wnt Signaling Pathway / drug effects
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism

Substances

  • Ropivacaine
  • Angiotensin-Converting Enzyme 2
  • ACE2 protein, human
  • Wnt1 Protein
  • WNT1 protein, human