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Amide-linked local anesthetics induce apoptosis in human non-small cell lung cancer
Hong-Wei Wang1, Le-Yi Wang1, Li Jiang1
1Department of Anesthesiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Background:
A retrospective analysis of patients undergoing cancer surgery suggested that using local anesthetics could reduce cancer recurrence and improve survival rate. Previous studies have indicated that local anesthetics may induce apoptosis in several kinds of cells in vitro, but the mechanism is unclear.
Methods:
Cell viability was analyzed by MTS; reactive oxygen species (ROS), mitochondrial membrane potential (MMP, ∆Ψm), cell cycle distribution, and cell apoptosis assay were detected by flow cytometry; DNA damage was measured by comet assay; cell invasion and migration were observed by microscopy; The expression level of related proteins was detected by western blot assay.
Results:
The results indicated that lidocaine and ropivacaine could decrease viability, induce G0/G1 phase arrest and apoptosis in human non-small cell lung cancer (NSCLC) cells A549 and H520. Invasion and migration were suppressed. Western blot indicated the related apoptotic pathways proteins changed accordingly. Additionally, lidocaine and ropivacaine downregulated ∆Ψm, provoked DNA damage, upregulated ROS production and activated mitogen-activated protein kinase (MAPK) pathways in A549 and H520 cells.
Conclusions:
The cytotoxic effect of amide-linked local anesthetics on NSCLC cells were mainly due to apoptosis. The antitumor mechanism of lidocaine and ropivacaine may involve apoptotic pathways and MAPK pathways.
Insights
Amide-linked local anesthetics like lidocaine and ropivacaine induce apoptosis and inhibit growth in non-small cell lung cancer (NSCLC) cells. Their antitumor effects involve activating apoptotic and mitogen-activated protein kinase (MAPK) pathways.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Retrospective cancer surgery analysis suggests local anesthetics may reduce recurrence and improve survival.
- Previous in vitro studies indicate local anesthetics can induce apoptosis, but mechanisms remain unclear.
Purpose of the Study:
- To investigate the cytotoxic effects and underlying mechanisms of amide-linked local anesthetics on non-small cell lung cancer (NSCLC) cells.
- To explore the role of apoptosis and MAPK signaling in the antitumor activity of lidocaine and ropivacaine.
Main Methods:
- Assessed cell viability (MTS), apoptosis, cell cycle, ROS, and mitochondrial membrane potential (MMP) via flow cytometry.
- Measured DNA damage (comet assay), cell invasion/migration (microscopy), and protein expression (Western blot).
Main Results:
- Lidocaine and ropivacaine decreased viability, induced G0/G1 arrest and apoptosis in A549 and H520 NSCLC cells.
- These agents suppressed cell invasion and migration, downregulated MMP, induced DNA damage, upregulated ROS, and activated MAPK pathways.
Conclusions:
- The primary cytotoxic effect of amide-linked local anesthetics on NSCLC cells is apoptosis induction.
- Antitumor mechanisms of lidocaine and ropivacaine involve apoptosis and MAPK signaling pathways.
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