Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4

Sep 24, 2026

Ropivacaine is a local anesthetic widely used for perioperative pain control during lung cancer surgery, and accumulating evidence supports its antitumor potential. Prior work showed ropivacaine suppresses malignant behavior of lung cancer cells in vitro, but the specific targets involved in this effect remain insufficiently defined. This study investigated how ropivacaine modulates antitumor mechanisms in lung cancer by identifying ropivacaine-triggered differentially expressed proteins and determining key functional mediators in A549 and H1299 cells.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

Submitted 26 June 2023 Accepted 25 October 2023 Published 27 November 2023 Corresponding author Huiqun Jia, [jysyjiahuiqun@163.com](jysyjiahuiqun@163.com)[ ](jysyjiahuiqun@163.com)Academic editor Abhishek Tyagi Additional Information and Declarations can be found on page 16 DOI 10.7717/peerj.16471 Copyright 2023 Jia et al. Distributed under Creative Commons CC-BY 4.0 OPEN ACCESS Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4 Weiai Jia1 ,* , Junmei Shen1 ,* , Sisi Wei2 , Chao Li1 , Jingpu Shi1 , Lianmei Zhao2 and Huiqun Jia1 1 Department of Anesthesiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China 2 Scientific Research Center, The Forth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China * These authors contributed equally to this work. ABSTRACT Background. Ropivacaine is a local anesthetic commonly used in regional nerve blocks to manage perioperative pain during lung cancer surgery. Recently, the antitumor potential of ropivacaine has received considerable attention. Our previous study showed that ropivacaine treatment inhibits the malignant behavior of lung cancer cells in vitro. However, the potential targets of ropivacaine in lung cancer cells have not yet been fully identified. This study aimed to explore the antitumor effects and mechanisms of action of ropivacaine in lung cancer. Methods. Lung cancer A549 cells were treated with or without 1 mM ropivacaine for 48 h. Quantitative proteomics was performed to identify the differentially expressed proteins (DEPs) triggered by ropivacaine treatment. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and analyze the most significant hub genes. Overexpression plasmids and small interfering RNA were used to modulate the expression of key DEPs inA549 and H1299 cells. MTS, transwell assays, and flow cytometry were performed to determine whether the key DEPs were closely related to the anticancer effect of ropivacaine on the malignant behavior of A549 and H1299 cells. Results. Quantitative proteomic analysis identified 327 DEPs (185 upregulated and 142 downregulated proteins) following ropivacaine treatment. Retinoblastoma-binding protein 4 (RBBP4) was one of the downregulated DEPs and was selected as the hub protein. TCGA database showed that RBBP4 was significantly upregulated in lung cancer and was associated with poor patient prognosis. Inhibition of RBBP4 by siRNA resulted in a significant decrease in the proliferation and invasive capacity of lung cancer cells and the induction of cell cycle arrest. Additionally, the results indicated RBBP4 knockdown enhanced antitumor effect of ropivacaine on A549 and H1299 cells. Conversely, the overexpression of RBBP4 using plasmids reversed the inhibitory effects of ropivacaine. Conclusion. Our data suggest that ropivacaine suppresses lung cancer cell malignancy by downregulating RBBP4 protein expression, which may help clarify the mechanisms underlying the antitumor effects of ropivacaine. How to cite this article Jia W, Shen J, Wei S, Li C, Shi J, Zhao L, Jia H. 2023. Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4. PeerJ 11:e16471 [http://doi.org/10.7717/peerj.16471](http://doi.org/10.7717/peerj.16471) Subjects Biochemistry, Bioinformatics, Cell Biology, Molecular Biology, Oncology Keywords Ropivacaine, Lung cancer, RBBP4, Proteomics, Malignant behavior INTRODUCTION Lung cancer is a widespread malignancy and the leading cause of cancer-related fatalities worldwide (Miller et al., 2022; Zheng et al., 2022) . According to global cancer statistics, an estimated 2.2 million new cases and 1.8 million deaths from lung cancer were recorded in 2020 (Sung et al., 2021) . Surgical resection remains the primary treatment for early-stage lung cancer. However, postoperative recurrence and

FAQs

What is the purpose of this study on ropivacaine in lung cancer cells?

To explore the antitumor effects and underlying mechanisms of ropivacaine in lung cancer, including identification of relevant molecular targets.

How were lung cancer cells treated and which assays were used?

Lung cancer A549 cells were treated with or without 1 mM ropivacaine for 48 h. Quantitative proteomics identified differentially expressed proteins, and assays including MTS, transwell, and flow cytometry assessed proliferation, invasion, and related phenotypes.

What role does RBBP4 play in the effects of ropivacaine?

RBBP4 was downregulated by ropivacaine, and inhibiting RBBP4 via siRNA reduced proliferation and invasive capacity while inducing cell cycle arrest; RBBP4 overexpression reversed ropivacaine’s inhibitory effects.

Sep 24, 2026

Upload by Mary Man