TY - JOUR AU - Gong, Xiaodan AU - Dan, Jiapeng AU - Li, Fang AU - Wang, Lishen PY - 2018 TI - Suppression of mitochondrial respiration with local anesthetic ropivacaine targets breast cancer cells JF - Journal of Thoracic Disease; Vol 10, No 5 (May 31, 2018): Journal of Thoracic Disease Y2 - 2018 KW - N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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. UR - https://jtd.amegroups.org/article/view/21262