Lidocaine Regulates the Proliferation and Apoptosis of Colorectal Cancer Cells by Modulating AKR1B1/miR-21-5p Pathway

¹ Department of Anesthesiology, The Affiliated Huai’an Hospital of Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an 223022, Jiangsu, China,

PAR 2026 , 10(3), 1–11; https://doi.org/10.26689/par.v10i3.14288

© 2026 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

This study was to investigate the effect of lidocaine on the proliferation and apoptosis of the human colorectal carcinoma cell line (HCT116) and explore the underlying mechanism. HCT116 cells’ proliferation and apoptosis rate were determined by CCK8 assay flow cytometry, followed by treating the cells with 0.5 mM and 1 mM lidocaine. HCT116 cells were transfected with NC-mimic, Mimic-miR-21-5p, inhibitor-NC, and Inhibitor-miR-21-5p, followed by treatment with Lidocaine and fidarestat, combined and both alone. The expression of miR-21-5p and of AKR1B1, PTEN, p-AKT, AKT, and PI3K proteins was determined by qRT-PCR and Western blot. This study find lidocaine inhibited cell proliferation and promoted apoptosis in a time-dose dependent manner. Lidocaine and fidarestat, both alone and in combination, reduced the expression of miR-21-5p and AKR1B1. Lidocaine and fidarestat alone and combined treatments and the miR-21-5p-inhibitor group decreased the expression of p-AKT and PI3K and vice versa in the mimic-miR-21-5p group. The expression of PTEN was increased in the lidocaine + fidarestat group, decreased in the mimic-miR-21-5p group. These results suggest that lidocaine inhibited the proliferation of HCT116 cells and promoted cell apoptosis by downregulating the expression of AKR1B1/miR-21-5p and further modulating the PTEN/AKT/PI3K signaling pathway.

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