Amide-linked local anesthetics induce apoptosis in human non-small cell lung cancer

Abstract

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.

Antitumor Effects of Lidocaine on Human Breast Cancer Cells: An In Vitro and In Vivo Experimental Trial

“…These results suggest that the mechanisms of action of lidocaine on cell viability are different among distinct cell lines. These results are consistent with findings of breast (16,19,22) and other cancer cell types including A549 and H520 human non-small cell lung cancer cells (20), 8505C and K1 human thyroid cancer cells (17), PC-3 prostatic cancer cells and ES-2 ovarian cancer cells (19).…”

“…Perioperative intravenous lidocaine infusion has been shown to reduce postoperative pain and opioid requirements (14,15). Lidocaine has also been shown to induce apoptosis and suppress tumor growth in human breast tumor cells (16) as well as other in vitro tumor cells (12,(17)(18)(19)(20)(21). Additionally, it has been reported to enhance sensitization of breast cancer cells to chemotherapeutic drugs (22).…”

Ropivacaine inhibits proliferation, invasion, migration and promotes apoptosis of papillary thyroid cancer cells via regulating ITGA2 expression

“…For instance, they can facilitate the apoptosis of human thyroid cancer cells via regulation of the mitogen-activated protein kinase pathway (Chang et al, 2014). Compelling evidence has indicated that Amide-linked local anesthetics contributes to apoptosis of human nonsmall cell lung cancer (Wang et al, 2016). Lidocaine plays significant roles in inhibiting proliferation and promoting apoptosis of F I G U R E 6 ITGA2 overexpression alleviated the effect of Ropivacaine on apoptosis of TPC-1 cells.…”

Effects of Lidocaine and Ropivacaine on Gastric Cancer Cells Through Down-regulation of ERK1/2 Phosphorylation In Vitro

“…In addition, in vitro and in vivo studies showed that LAs might also have direct effects on certain tumour cells (e.g. breast, lung, liver and thyroid) (15)(16)(17)(18). It has been reported that lidocaine inhibited the growth of HepG2 cells in a dose-dependent and time-dependent manner, arrested cells in the G 0 /G 1 phase of the cell cycle and induced apoptosis (19).…”