Abstract
BackgroundRecent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote apoptosis of hepatocellular carcinoma (HCC) cells is still unclear. The aim of this study was to investigate the effect of ropivacaine on the apoptosis of HCC cells.MethodsIn the present study, we treated the HCC cell lines, Bel7402 and HLE with ropivacaine. MTT, DAPI stain, trypan blue exclusion dye assay, flow cytometry, electron microscopy, computational simulation, laser confocal microscope, Western blotting, and enzyme activity analysis of caspase-3 were applied to detect the growth and apoptosis of HCC cells and to explore the role mechanism of ropivacaine.ResultsRopivacaine was able to inhibit proliferation and promote apoptosis of HCC cells in a dose- and time-dependent manner. Ropivacaine also has a trait to inhibit the migration of HCC cells; ropivacaine damaged the mitochondria of HCC cells. The results also indicated that ropivacaine was able to interact with caspase-3, promote cytoplasmic caspase-3 migration into the nucleus, stimulate cleavage of caspase-3 and PARP-1, caspase-9 proteins, inhibit the expression of Bcl-2, promote expression of Apaf-1 and mitochondria release cytochrome C, and activate the activity of caspase-3.ConclusionsRopivacaine has a novel role in promoting apoptosis of HCC cells; The role mechanism of ropivacaine maybe involve in damaging the function of mitochondria and activating the caspase-3 signalling pathway in HCC cells. Our findings provide novel insights into the local anaesthetic agents in the therapy of HCC patients.
Highlights
Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote apoptosis of hepatocellular carcinoma (HCC) cells is still unclear
Ropivacaine inhibited the growth of HCC cells In the study, we treated with human hepatoma cell lines, Bel 7402 and HLE of difference concentrations of ropivacaine (0.25, 0.5, 1.0, 2.0 and 4.0 mmol/L) for 24, 48, 72 h respectively, and the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was applied to detect the growth of these HCC cells
Ropivacaine promotes apoptosis of HCC cells To explore the effect of ropivacaine on the apoptosis of HCC cells, in the present investigation, Bel 7402 cells and HLE cells were treated with different concentrations of ropivacaine (0.5, 1.0, 2.0 mmol/L) for 48 h
Summary
Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote apoptosis of hepatocellular carcinoma (HCC) cells is still unclear. Local anaesthetic agents have broad therapeutic functions that go beyond the known analgesia and antiarrhythmic [1] They are applied in a wide range of clinical situations to prevent or reduce acute pain, chronic pain. Recent evidences indicated that lidocaine played a role in anti-proliferation and induced apoptosis of hepatocellular carcinoma (HCC) cells [14, 15], which implicated that local anaesthetics can suppress the growth of HCC cells. Several studies have focused on the potential cytotoxic effects of ropivacaine on HCC cells [14, 15] The evidence from these studies showed that ropivacaine inhibits the viability of HCC cells in a dose- and time-dependent manner. We found that ropivacaine was capable of inhibiting viability, stimulating apoptosis of HCC cells, damaging mitochondria, and activating the activity of caspase-3 in HCC cells
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