Ropivacaine Inhibits Lung Cancer Cell Malignancy Through Downregulation of Cellular Signaling Including HIF-1α In Vitro

Abstract

Background: Ropivacaine is widely used to induce regional anesthesia during lung cancer surgery. Previous studies reported that amide-linked local anesthetics, e.g., ropivacaine, affected the biological behavior of lung adenocarcinoma cells, but the conclusion is controversial and warrants further study. This study set out to investigate the biological effects of ropivacaine on cultured lung cancer cells and underlying mechanisms.Methods: Lung cancer cell lines (A549 and H1299) were cultured and then treated with or without ropivacaine (0.5, 1, and 2 mM) for 48 or 72 h. Their proliferation, migration, and invasion together with cell death and molecules including hypoxia inducible factor (HIF)-1α, VEGF, matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 expression associated with these changes were determined.Results: Ropivacaine significantly inhibited proliferation and migration, invasion, and cell death in a concentration-dependent manner in both cell lines. Ropivacaine also promoted cell death and induced a concentration- and time-dependent cell arrest towards the G0/G1 phase. Expression of VEGF, MMP-1, MMP-2, MMP-9, and HIF-1α in both cell lines was also inhibited by ropivacaine in a concentration-related manner.Conclusion: Our data indicated that ropivacaine inhibited lung cancer cell malignancy, which may be associated with downregulation of cell-survival-associated cellular molecules. The translational value of the current work is subjected to further study.

Ropivacaine combined with sorafenib attenuates hepatocellular carcinoma cell proliferation and metastasis by inhibiting the miR‐224/HOXD10 axis

“…Rop is one of the latest amide anesthetics used vastly in local anesthesia, which is generally considered safe for human use 25 . Clinical data confirm that Rop is effective in reducing cancer recurrence and metastasis of various cancers 26 . Here, the combination of Rop and Sor was superior to either Rop or Sor alone in inhibiting the malignant behavior of HCC cells.…”

“…25 Clinical data confirm that Rop is effective in reducing cancer recurrence and metastasis of various cancers. 26 Here, the com- Knowledge of the interaction of miRNAs and mRNAs suggest that miRNAs regulate their targets. Accordingly, we first analyzed the levels of miR-224's possible target HOXD10, and the expression of HOXD10 was opposite to that of miR-224 in HCC cells.…”

Ropivacaine inhibits the proliferation and metastasis of gastric cancer cells via the SNX10/SRC/STAT3 pathway

“…Rop is the most commonly used local anesthetic for the relief of acute pain, chronic pain, and cancer pain (Kuthiala & Chaudhary, 2011;Li et al, 2017;Zhang, Zhu, et al, 2020). The antitumor effects of Rop have been proved in gastric cancer (Shen et al, 2021), lung cancer (Nabeshima et al, 2002), and hepatocellular cancer (Wang et al, 2019;Zhang et al, 2021). Wang et al (2019) reported that Rop promoted apoptosis of hepatocellular carcinoma cells through damaging mitochondria and activating caspase-3 activity.…”

“…Among them, MMP‐2 and MMP‐9 are closely related to tumor invasion and metastasis (Deryugina et al., 1997; Veeravalli & Rao, 2012; Webb et al., 2017). Rop has been reported to inhibit tumor cell invasion and MMP‐9 secretion (Shen et al., 2021). In our study, we showed that Rop reduced the expression of both MMP‐9 and MMP‐2 simultaneously.…”

Trial watch: local anesthetics in cancer therapy

“… 24 Additionally, LAs may impact on matrix metalloproteinases (MMPs), retarding the dissemination of tumor cells through the extracellular space and thus decreasing the invasion of distant organs. 11 , 23 , 25 , 26 …”