Suppression of mitochondrial respiration with local anesthetic ropivacaine targets breast cancer cells

Retrospective studies on cancer patients who have received local anesthesia show a favorable decrease in tumor metastasis and recurrence. However, the mechanisms underlying the benefits of local anesthesia on cancer recurrence are not well understood. In this study, we investigated the biological ef...

Full description

Saved in:
Bibliographic Details
Published inJournal of thoracic disease Vol. 10; no. 5; pp. 2804 - 2812
Main Authors Gong, Xiaodan, Dan, Jiapeng, Li, Fang, Wang, Lishen
Format Journal Article
LanguageEnglish
Published China AME Publishing Company 01.05.2018
Subjects
Original
ropivacaine
Breast cancer
Akt/mTOR
mitochondrial respiration
Online AccessGet full text

Cover

More Information
Summary:Retrospective studies on cancer patients who have received local anesthesia show a favorable decrease in tumor metastasis and recurrence. However, the mechanisms underlying the benefits of local anesthesia on cancer recurrence are not well understood. In this study, we investigated the biological effects of ropivacaine on breast cancer cells and the mechanisms of its action with emphasis on mitochondrial respiration. Ropivacaine significantly inhibited growth, survival, and anchorage-independent colony formation in two human breast cancer cell lines. It also acted synergistically with a 5-FU in breast cancer cells. Mechanistically, ropivacaine was found to inhibit mitochondrial respiration by suppressing mitochondrial respiratory complex I and II activities, leading to energy depletion, and oxidative stress and damage. The inhibitory effects of ropivacaine in breast cancer cells were abolished in mitochondrial respiration-deficient ρ0 cells, indicating that mitochondrial respiration is essential for the mechanism of action of ropivacaine. Ropivacaine inhibited phosphorylation of Akt, mTOR, rS6, and EBP1 in breast cancer cells, suggesting the association between Akt/mTOR signaling pathway and mitochondrial functions in breast cancer. Our work clearly demonstrates the inhibitory effects of ropivacaine in breast cancer by disrupting mitochondrial function. Our findings provide a proper understanding of how local anesthetics reduce the risk of tumor recurrence, and thus, support the use of ropivacaine for surgery and to control pain in patients with breast cancer.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Contributions: (I) Conception and design: X Gong, L Wang; (II) Administrative support: F Li; (III) Provision of study materials or patients: X Gong, J Dan, F Li; (IV) Collection and assembly of data: X Gong, J Dan, L Wang; (V) Data analysis and interpretation: X Gong, J Dan, L Wang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
These authors contributed equally to this work.
ISSN:2072-1439
2077-6624
DOI:10.21037/jtd.2018.05.21