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

• Published in: International journal of molecular sciences Vol. 25; no. 17; p. 9334
• Main Authors: Iwasaki, Masae, Yamamoto, Makiko, Tomihari, Masahiro, Ishikawa, Masashi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.08.2024
• Subjects: 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; Biology; Cancer therapies; Cell adhesion & migration; Cell growth; Cell Movement - drug effects; Cell Proliferation - drug effects; Cluster analysis; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; General anesthesia; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical prognosis; Mortality; Radiation therapy; Ropivacaine - pharmacology; Up-Regulation - drug effects; Wnt Signaling Pathway - drug effects; Wnt1 Protein - genetics; Wnt1 Protein - metabolism; ropivacaine; ACE2; Wnt1 pathway; HIF1α; PCR array
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25179334

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.