Propofol Treatment Research Articles

Propofol‑induced HOXA11‑AS promotes proliferation,migration and invasion, but inhibits apoptosis inhepatocellular carcinoma cells by targeting miR‑4458.

Propofol is a commonly used drug for the induction and maintenance of anesthesia. Previous studies have reported that propofol is involved in the progression of numerous human cancer types, including hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms in HCC are yet to be elucidated. The present study aimed to investigate the potential mechanism of propofol in HCC development. MTT assay, flow cytometry analysis and Transwell assays were conducted to examine cell proliferation, apoptosis, migration and invasion, respectively. Western blotting was also performed to determine the protein expression levels of Bcl-2 and cleaved-caspase 3. An in vivo experiment was performed to assess the effect of propofol on tumor growth. Moreover, reverse transcription-quantitative PCR was conducted to measure the mRNA expression levels of HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS) and microRNA (miR)-4458. Dual-luciferase reporter and RNA pull-down assays were performed to evaluate the target relationship between HOXA11-AS and miR-4458. It was demonstrated that propofol inhibited HCC cell proliferation, migration and invasion, and promoted cell apoptosis in vitro. Furthermore, propofol could suppress tumor growth in vivo. Propofol suppressed the expression of HOXA11-AS in HCC cells, while HOXA11-AS overexpression reversed the inhibitory effect of propofol treatment on cell progression in HCC. In addition, miR-4458 was identified as a target of HOXA11-AS, and miR-4458 inhibition reversed the effect of HOXA11-AS knockdown on HCC cell progression. The results also indicated that propofol promoted the expression of miR-4458, while HOXA11-AS restored this effect in HCC. Thus, it was suggested that propofol suppressed cell progression by modulating the HOXA11-AS/miR-4458 axis in HCC.

Assessment of the sedative effects of dexmedetomidine and propofol treatment in patients undergoing mechanical ventilation in the ICU and relationship between treatment and occurrence of ventilator-associated pneumonia and detection of pathogenic bacteria.

The present study aimed to investigate the sedative effects of dexmedetomidine combined with propofol in patients undergoing mechanical ventilation in the intensive care unit (ICU), and to reveal the risk factors of ventilator-associated pneumonia (VAP). A retrospective analysis of 322 patients who had been subject to mechanical ventilation in the ICU ward was performed. Subjects were divided into two groups: A group treated with dexmedetomidine and propofol (combined group) and a group treated with dexmedetomidine alone (monotherapy group). Clinical data, sedative effects, the number of VAP patients and the distribution of VAP pathogens were assessed. Multivariate analysis and receiver operating characteristic (ROC) curves were used to predict VAP. Significant differences in the sedative effects between the two groups were observed (P<0.001). The incidence of VAP was significantly higher in the monotherapy group compared with the combined group (P<0.05). Multivariate logistic regression analysis demonstrated that age, acute physiology chronic health evaluation score, consciousness, invasive operations, recovery time, extubation time and sedation regimen were independent risk factors for VAP in the ICU during mechanical ventilation. ROC curves indicated that the areas under the curve for age, acute physiology chronic health score, consciousness, invasive operations, recovery time, extubation time and sedation regimen were 0.934, 0.870, 0.632, 0.677, 0.865, 0.950 and 0.603, respectively. In summary, dexmedetomidine combined with propofol can shorten the recovery and extubation times of mechanical ventilation patients in the ICU. Different sedation schemes are also independent risk factors for VAP during mechanical ventilation in the ICU.

Propofol Affects Non-Small-Cell Lung Cancer Cell Biology By Regulating the miR-21/PTEN/AKT Pathway In Vitro and In Vivo.

Propofol is a common sedative-hypnotic drug traditionally used for inducing and maintaining general anesthesia. Recent studies have drawn attention to the nonanesthetic effects of propofol, but the potential mechanism by which propofol suppresses non-small-cell lung cancer (NSCLC) progression has not been fully elucidated. For the in vitro experiments, we used propofol (0, 2, 5, and 10 µg/mL) to treat A549 cells for 1, 4, and 12 hours and Cell Counting Kit-8 (CCK-8) to detect proliferation. Apoptosis was measured with flow cytometry. We also transfected A549 cells with an microribonucleic acid-21 (miR-21) mimic or negative control ribonucleic acid (RNA) duplex and phosphatase and tensin homolog, deleted on chromosome 10 (PTEN) small interfering ribonucleic acid (siRNA) or negative control. PTEN, phosphorylated protein kinase B (pAKT), and protein kinase B (AKT) expression were detected using Western blotting, whereas miR-21 expression was examined by real-time polymerase chain reaction (RT-PCR). In vivo, nude mice were given injections of A549 cells to grow xenograft tumors; 8 days later, the mice were intraperitoneally injected with propofol (35 mg/kg) or soybean oil. Tumors were then collected from mice and analyzed by immunohistochemistry and Western blotting. Propofol inhibited growth (1 hour, P = .001; 4 hours, P ≤ .0001; 12 hours, P = .0004) and miR-21 expression (P ≤ .0001) and induced apoptosis (1 hour, P = .0022; 4 hours, P = .0005; 12 hours, P ≤ .0001) in A549 cells in a time and concentration-dependent manner. MiR-21 mimic and PTEN siRNA transfection antagonized the suppressive effects of propofol on A549 cells by decreasing PTEN protein expression (mean differences [MD] [95% confidence interval {CI}], -0.51 [-0.86 to 0.16], P = .0058; MD [95% CI], 0.81 [0.07-1.55], P = .0349, respectively), resulting in an increase in pAKT levels (MD [95% CI] = -0.82 [-1.46 to -0.18], P = .0133) following propofol exposure. In vivo, propofol treatment reduced NSCLC tumor growth (MD [95% CI] = -109.47 [-167.03 to -51.91], P ≤ .0001) and promoted apoptosis (MD [95% CI] = 38.53 [11.69-65.36], P = .0093). Our study indicated that propofol inhibited A549 cell growth, accelerated apoptosis via the miR-21/PTEN/AKT pathway in vitro, suppressed NSCLC tumor cell growth, and promoted apoptosis in vivo. Our findings provide new implications for propofol in cancer therapy and indicate that propofol is extremely advantageous in surgical treatment.

Effects of propofol on invasion and migration of colon cancer cells and JAK2/STAT3 signaling pathway.

To investigate the effect of propofol on invasion and migration of human colon cancer cell line SW480 and the JAK2/STAT3 pathway. Human colon cancer cell line SW480 was divided into a control group, 3 propofol treatment groups (with 2, 4 and 8 μg/mL propofol treatment, respectively), and a propofol+colivelin group. Lactate dehydrogenase (LDH) activity and cell proliferation was evaluated by detection kit and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, respectively. Cell migration and invasion were detected by Transwell assay. Western blotting was performed to detect the protein expression levels of JAK2, p-JAK 2, STAT3 and p-STAT3 in colon cancer cell line SW480. Compared with the control group, the LDH activity was significantly increased in the propofol treatment groups (P<0.05). The cell proliferation, migration, invasion as well as p-JAK2 and p-STAT3 in colon cancer cell line SW480 in the propofol treatment groups were significantly decreased (allP<0.05). Compared with the propofol treatment groups, the p-STAT3 level, proliferation, migration and invasion in the colon cancer cell line SW480 were significantly increased in the propofol+colivelin group (allP<0.05). Propofol can inhibit the proliferation, migration and invasion of human colon cancer cells by inhibiting JAK2/STAT3 signaling pathway.

Propofol inhibited apoptosis of hippocampal neurons in status epilepticus through miR-15a-5p/NR2B/ERK1/2 pathway

ABSTRACTAlthough a previous study reported that propofol had a therapeutic effect in status epilepticus (SE), the mechanisms underlying the effect of propofol in SE remain unclear. The aim of this study was to explore the regulatory mechanisms underlying propofol-induced inhibition of SE.A rat SE model was established using the lithium–pilocarpine injection method. A qRT-PCR and Western blot were utilized to detect the expression of relative molecules. Cell apoptosis was evaluated by a flow cytometry assay. The interaction between miR-15a-5p and NR2B was assessed using a luciferase reporter assay.Propofol inhibited cell apoptosis and increased miR-15a-5p expression both in hippocampal tissues of SE rats and low Mg2+-induced hippocampal neurons. Propofol-induced attenuation of apoptosis of low Mg2+-induced hippocampal neurons was mediated by miR-15a-5p. miR-15a-5p targeted NR2B and negatively regulated its expression. Propofol downregulated NR2B expression, mediated by miR-15a-5p. In terms of the mechanism of action, propofol suppressed the apoptosis of Mg2+-induced hippocampal neurons through the miR-15a-5p/NR2B/ERK1/2 pathway. In vivo experiment suggested that propofol inhibited the apoptosis of hippocampal neurons in SE rats by upregulating miR-15a-5p.In terms of the molecular mechanism of propofol, it appears to inhibit apoptosis of hippocampal neurons in SE through the miR-15a-5p/NR2B/ERK1/2 pathway. The findings provide theoretical support for propofol treatment of SE.

Propofol alleviates ventilator-induced lung injury through regulating the Nrf2/NLRP3 signaling pathway

Ventilator-induced lung injury (VILI) causes problems during acute lung injury treatment, and propofol is a well-known drug to prevent VILI. Herein, we discussed how propofol protects against VILI-induced inflammation with the interaction of nuclear factor E2-related factor 2 (Nrf2)/NOD-like receptor protein 3 (NLRP3). We established VILI mouse models for collecting lung tissues, and these mice were later treated with propofol and Nrf2/NLRP3 activator or inhibitor to observe their effects on VILI with inflammatory factors, 8-hydroxy-2 deoxyguanosine, malondialchehyche level, mitochondrial reactive oxygen species production rate, lung wet/dry weight ratio, lung permeability index measured. Propofol treatment improved VILI, alleviated pulmonary inflammation induced by mechanical ventilation. Propofol up-regulated Nrf2 and down-regulated NLRP3 in VILI model. Activating Nrf2 or inhibiting NLRP3 downregulated pro-inflammatory factors in lung tissues in VILI mice. Above all, we can conclude that propofol exerts it protective function against VILI and the subsequent inflammatory responses through activating Nrf2 and inhibiting NLRP3 expression. Therefore, Nrf2 activator and NLRP3 inhibitor might be latent targets in the VILI prevention.

Irisin ameliorates the postoperative depressive-like behavior by reducing the surface expression of epidermal growth factor receptor in mice

Postoperative depression is a serious problem with under-optimized treatment. Our previous result demonstrated that single dose of propofol exposure in mice could cause depressive-like behavior. In the present study, we explored the possible preventive strategy that could ameliorate the depressive-like behavior in mice. Irisin was used for co-treatment with propofol in mice to test whether irisin could prevent the depressive-like behavior in mice. We found irisin could significantly reduce the immobility time in tail suspension and forced swimming tests in mice with propofol. We also found irisin was able to protect neurons against high concentration propofol treatment induced cell death in cultures. Meanwhile, irisin could significantly inhibit the increase of cytokines in astrocyte cultures exposed to propofol. These in vitro results suggested that interaction between astrocyte and neuron may be involved in the action mechanism that irisin prevented the mice from developing of depressive-like behavior. Last, we revealed that propofol caused increased surface expression of epidermal growth factor receptor (EGFR) but irisin could reduce the expression level of EGFR on cell surface.

Propofol Improves Sensitivity of Lung Cancer Cells to Cisplatin and Its Mechanism.

BackgroundCisplatin (cis-diamminedichloroplatinum, DDP) resistance is identified as the primary obstacle during lung cancer treatment, while DDP resistance is exist extensively. This report was to investigate the roles of propofol in lung cancer cells tolerance to DDP and the potential mechanisms.Material/MethodsA549 and A549/DDP cells were treated with DDP for 48 hours, and cell proliferation suppression rate was detected by MTT (thiazolyl blue tetrazolium bromide) assay and half maximal inhibitory concentration (IC50) of DDP to lung cancer cells was calculated. Besides, cell proliferation and apoptosis were determined by MTT assay and flow cytometry assay respectively in propofol-treated A549/DDP and A549 cells. Furthermore, we performed MTT assay to determine the influence of propofol on the sensitivity of lung cancer cells to DDP.ResultsThe results demonstrated that the IC50 of DDP to A549 cells was lower than that in A549/DDP cells. Propofol dramatically inhibited cell proliferation and promoted cell apoptosis of A549/DDP and A549 cells. In addition, propofol significantly improved the anti-proliferative impact of DDP in A549/DDP and A549 cells, and the value of IC50 for DDP in the A549/DDP and A549 cells were decreased after propofol treatment compare to the control group. Moreover, propofol inhibited the Wnt/β-catenin pathway in a dose-dependent manner in both A549/DDP and A549 cells.ConclusionsOur report indicated that propofol could control lung cancer cell proliferation and apoptosis, and stimulated the suppression function of DDP on lung cancer cell multiplication via the Wnt/β-catenin signaling pathway, and also provided a new treatment for DDP tolerance to cure lung cancer in clinical.

Propofol Reduces Epithelial to Mesenchymal Transition, Invasion and Migration of Gastric Cancer Cells through the MicroRNA-195-5p/Snail Axis.

BackgroundGastric cancer (GC) is a life-threating malignancy worldwide. Accumulating studies suggest propofol has anti-tumor functions in addition to the anesthetic effect. This study aimed to figure out the effects of propofol treatment in GC development.Material/MethodsHuman GC SGC-7901 and NCI-N87 cells were treated with different doses of propofol. Then the invasion and migration of GC cells was measured. SGC-7901 cells following 10 μM propofol treatment were applied in the following experiments. MicroRNAs (miRNAs) with differential expression in cells with or without propofol treatment were analyzed. Expression of miR-195-5p, Snail, vimentin and E-cadherin in SGC-7901 cells was measured, and then loss-of-function of miR-195-5p and gain-of-function of Snail were performed. Target relation between miR-195-5p and Snail was confirmed using luciferase assay. Xenograft tumor was induced in nude mice to identify the effect of propofol on GC in vivo.ResultsPropofol reduced epithelial to mesenchymal transition (EMT), invasion and migration of GC cells in a dose-dependent manner. Propofol elevated miR-195-5p expression but reduced Snail expression, and it reduced vimentin but increased E-cadherin expression in SGC-7901 cells. miR-195-5p directly bound to Snail. miR-195-5p inhibition or Snail promotion reversed propofol-inhibited malignant behaviors of SGC-7901 cells. In vitro results were reproduced in in vivo experiments.ConclusionsOur study found that propofol could inhibit EMT, invasion, and migration of GC cells by promoting miR-195-5p expression and suppressing Snail expression. This study may provide novel insights in GC treatment.

Effects of propofol on colon cancer metastasis through STAT3/HOTAIR axis by activating WIF‐1 and suppressing Wnt pathway

BackgroundIn the present study, we aim to investigate the potential role of propofol in the tumor progression of colon cancer.MethodsHuman colon cancer cell lines were cultured and exposed with 8 μg/mL propofol. RNA interference was performed to silence the expression of HOTAIR or STAT3 to explore their biological functions in colon cancer. Cell apoptosis and invasion were assessed using flow cytometry and transwell assays, respectively. Quantitative real‐time PCR, western blot, and immunohistochemistry were subjected to measure the expression patterns of HOTAIR, STAT3, Wnt signaling factors, and epithelial‐mesenchymal transition‐related markers, respectively. Besides, nude mice were transplanted with colon cancer cells for further exploration. Tumor formation, volume, and weight were evaluated to validate the in vitro findings.ResultsPropofol treatment promoted cell apoptosis and inhibited cell invasion in colon cancer cells, while the effects were reversed by HOTAIR overexpression. Additionally, STAT3 positively regulated HOTAIR expression, which was also negatively modulated by propofol. Moreover, STAT3 and HOTAIR were shown to independently regulate colon cancer cell apoptosis and invasion. Furthermore, HOTAIR could stimulate Wnt signaling pathway via inhibiting WIF‐1 expression and upregulating β‐catenin expression, which was also demonstrated by in vivo study.ConclusionTaken together, the current study demonstrated that propofol exerts the inhibition on cell invasion and promotion on cell apoptosis through regulating STAT3/HOTAIR by activating WIF‐1 and suppressing Wnt pathway, indicating that propofol might serve as a therapeutic role for colon cancer patients in the future.

Propofol Inhibits Cell Proliferation, Migration, and Invasion via mir-410-3p/Transforming Growth Factor-β Receptor Type 2 (TGFBR2) Axis in Glioma.

BackgroundPropofol is a common intravenous anesthetic used to induce and maintain anesthesia. Numerous studies have reported that propofol plays an anti-tumor role in diverse human cancers, including glioma. In this research, we explored the roles of propofol and its related molecular mechanisms in glioma.Material/MethodsU251 and A172 cells were exposed to different doses of propofol for 24 h. Cell proliferation, migration, and invasion in glioma were evaluated using MTT assay and Transwell assay, respectively. The levels of microRNA-410-3p (miR-410-3p) and transforming growth factor-β receptor type 2 (TGFBR2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay and Western blot assay, respectively. The association between miR-410-3p and TGFBR2 was predicted by TargetScan and confirmed by dual-luciferase reporter assay.ResultsPropofol inhibited the proliferation, migration, and invasion of glioma cells in a concentration-dependent way. miR-410-3p was induced and TGFBR2 was inhibited by different concentrations of propofol treatment. Moreover, TGFBR2 was confirmed to be a target gene of miR-410-3p and TGFBR2 was inversely modulated by miR-410-3p in glioma cells. Depletion of miR-410-3p reversed the inhibition of propofol treatment on U251 and A172 cell growth and metastasis, but the effects were further abolished by knocking down the expression of TGFBR2.ConclusionsPropofol can suppress cell growth and metastasis by regulating the miR-410-3p/TGFBR2 axis in glioma.

Propofol protects human cardiac cells against chemical hypoxiainduced injury by regulating the JNK signaling pathways.

Propofol is a widely used intravenous anesthetic shown to exert a cardioprotective role against oxidative stress and ischemia/reperfusion injury in rat cardiac H9c2 cells. However, the regulatory mechanisms and functions of propofol in human cardiomyocytes remain unknown. The present study chemically induced hypoxia with cobalt chloride (CoCl2) to mimic cardiomyocyte ischemic injury in human cardiac AC16 and HCM cells. To investigate its underlying mechanisms, propofol was added to the cells before the chemical hypoxia phase. The present results suggested that, in response to hypoxia, mitochondrial membrane potential was lost, and cardiomyocyte viability and superoxide dismutase levels decreased. However, the present results showed that reactive oxygen species and malondialdehyde levels increased. The present results suggested that these effects were significantly reversed following propofol treatment. Additionally, the present results suggested that the protective effect of propofol against CoCl2-induced injury may be inhibited by the activation of the JNK signaling pathways. The present results indicated that propofol pre-treatment inhibited CoCl2-induced myocardial injury by preventing mitochondrial dysfunction, which may be partially due to the activation of the JNK signaling pathways. Therefore, propofol may exert anti-oxidative effects in human cardiac cells. The present results suggested that propofol may be used as a treatment for oxidative stress-related cardiac disorders.

Propofol suppresses proliferation and metastasis of colorectal cancer cells by regulating miR-124-3p.1/AKT3.

Propofol, an extensively used intravenous anesthetic agents during cancer resection surgery, has been confirmed to execute anti-tumor effect on multiple cancers, including colorectal cancer (CRC). Although the role of propofol in CRC has been previously reported, its action mechanism remains poorly understood. This study further explored the biological function and underlying mechanism of propofol in CRC cells. The cell proliferation, migration and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, wound healing assay and transwell assay, respectively. The expression levels microRNA-124-3p.1 (miR-124-3p.1) and AKT serine/threonine kinase 3 (AKT3) was analyzed by quantitative real-time polymerase chain reaction. Western blot assay was employed to measure the protein expression of MMP-9, Vimentin and Cyclin D1. The interaction between miR-124-3p.1 and AKT3 was predicted by TargetScan and confirmed by dual-luciferase reporter assay. Propofol inhibited CRC cell proliferation, migration and invasion. Knockdown of miR-124-3p.1 or AKT3 upregulation reversed the inhibitory effects of propofol on CRC cell proliferation and metastasis. Besides, AKT3 was a direct target of miR-124-3p.1 and its overexpression abated the anti-tumor effect of miR-124-3p.1 on CRC cell proliferation and metastasis. Propofol inhibited CRC cell proliferation, migration and invasion by upregulating miR-124-3p.1 and downregulating AKT3, providing a new sight for propofol treatment of CRC.

The Molecular Mechanisms Associated with the Effects of Propofol in a Rat Model of Pain Due to Inflammation Following Injection with Complete Freund's Adjuvant.

BackgroundThis study aimed to investigate the molecular mechanisms associated with the effects of propofol in a rat model of pain due to inflammation following subcutaneous injection with complete Freund’s adjuvant (CFA).Material/MethodsSprague-Dawley rats were injected subcutaneously in the paw with CFA. Propofol or saline was administered by tail vein injection. After CFA treatment for 0 hours, 4 hours, 1 day, 4 days, 7 days, and 14 days, the behavior of the rats was assessed. An enzyme-linked immunosorbent assay (ELISA) measured serum levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Western blot and the quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to detect levels of p38MAPK and NF-κB related mRNA and proteins, including p-p38, p38, p65, p-p65, NOD-like receptor family protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and caspase-1 in rat spinal cord tissues.ResultsInjection of CFA significantly reduced the mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), and frequency responses to cold stimulation. Propofol treatment significantly reduced serum levels of TNF-α, IL-1β, and IL-6. Protein expression levels of p-p38 and p-p65 were upregulated in the rat model, which were inhibited by propofol treatment. CFA injection increased the expression levels of NLRP3, ASC, and caspase-1 in the spinal cord tissues of rats, which were reduced by propofol treatment.ConclusionsIn a rat model of pain following subcutanous injection with CFA, propofol reduced CFA-induced pain and inhibited the inflammatory response through the p38MAPK-nuclear factor-κB (NF-κB) pathway and the NLRP3 inflammasome.

Propofol facilitates migration and invasion of oral squamous cell carcinoma cells by upregulating SNAI1 expression

AimTo investigate the effect of propofol on the migration and invasion of oral squamous cell carcinoma (OSCC) cells and explore the underlying mechanism. Main methodsCal-27 and SCC-25 cells treated with or without propofol, then the cells metastasis were determined. The levels of SNAI1 mRNA and protein were detected by real-time PCR and western blot. Cell migration ability was evaluated by wound healing assay, and the invasion of cells was measured using transwell assay. Key findingsPropofol treatment significantly promoted cell migration and invasion of OSCC. Further mechanistic studies of the stimulating effects of propofol on OSCC cell metastasis revealed that propofol treatment dose-dependently upregulated the expression of SNAI1, a member of the Snail superfamily of zinc-finger transcription factors. Additionally, the inhibition of endogenous SNAI1 expression reversed the effect of propofol on cell migration and invasion in Cal-27 and SCC-25 cells. SignificanceOur results demonstrate that propofol at clinically relevant concentrations facilitates cell migration and invasion through up-regulation of SNAI1 in OSCC cells, and suggest propofol may not be suitable for anesthesia management in OSCC patients.

Propofol for Treatment of Acute Migraine in the Emergency Department: A Systematic Review.

Propofol has not been extensively studied as an acute migraine therapy; however, based on the limited evidence from outpatient and inpatient settings, propofol has been proposed as an option for patients who present to the emergency department (ED). The purpose of this review was to evaluate the existing literature regarding the safety and efficacy of propofol for acute migraine treatment in the ED. A systematic review of clinical studies of propofol treatment for acute migraine in the ED was performed using Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Trials were identified through PubMed, Google Scholar, clinical trial registries, research registries, and key journals through May 2019. A modified Jadad scoring system was used to assess the methodologic quality of the included randomized controlled trials, and the Newcastle-Ottawa Scale was used for the retrospective cohort study. Nine studies, including five case reports or series, one retrospective cohort study, and three randomized controlled trials, consisting of 290 patients, were reviewed. All studies in adults reported propofol to be an effective therapy for migraine, but the strength of these results was limited by dosing variations, small sample sizes, and limited generalizability. Pediatric studies produced mixed results. Propofol may be an effective rescue therapy for patients presenting to the ED for acute migraine, but its place in therapy based on the limited available evidence is unknown. The safety of propofol for migraine management in the ED has not been adequately examined.

RETRACTED: Propofol weakens hypoxia-aroused apoptosis and autophagy via elevating microRNA-137 in neurocytes

Hypoxia was proven to cause brain cell apoptosis and autophagy. Herein, we tested the influences of propofol, a commonly used intravenous sedative hypnotic drug, on apoptosis and autophagy aroused by hypoxia stimulation in PC-12 and HT-22 cells. Followed by hypoxia and/or propofol treatment, cell viability of PC-12 and HT-22 cells, apoptosis and autophagy, along with microRNA-137 (miR-137) expression were measured, respectively. Then, miR-137 inhibitor was transfected to silence miR-137. Whether miR-137 took part in the impacts of propofol on hypoxia-exposed cells was explored. Finally, the activities of PI3K/AKT/mTOR and ERK pathways were measured. Hypoxia stimulation aroused cell apoptosis and elevated cell autophagy in PC-12 and HT-22 cells. Propofol weakened the apoptosis and autophagy of PC-12 and HT-22 cells aroused by hypoxia. Moreover, propofol elevated the miR-137 level in PC-12 and HT-22 cells. Silencing miR-137 declined the influences of propofol on hypoxia-induced injuries. Besides, propofol promoted PI3K/AKT/mTOR and ERK pathways activation in hypoxia-exposed cells through raising miR-137. Propofol weakened hypoxia-aroused apoptosis and autophagy of PC-12 and HT-22 cells might be through raising miR-137 level and thereby promoting PI3K/AKT/mTOR and ERK pathways activation.

Propofol Suppresses Proliferation, Migration, Invasion And Promotes Apoptosis By Upregulating microRNA-140-5p In Gastric Cancer Cells.

PurposeThis study aimed to investigate the anti-tumor effect of propofol on gastric cancer (GC) and its underlying mechanisms.Patients and methodsSGC-7901 and MKN45 cells were transfected and divided into the following groups: Control group, Propofol group, Propofol+miR-140-5p inhibitor group and miR-140-5p inhibitor group. Moreover, cell proliferation, apoptosis, migration and invasion of SGC-7901 and MKN45 cells were evaluated by BrdU incorporation assay, Annexin V-FITC/PI double staining assay, wound healing assay and transwell assay, respectively. The mRNA expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 were detected by qRT-PCR. Cleaved caspase-3, Bcl-2, MMP-2 and MMP-9 expressions were detected by Western blot.ResultsPropofol inhibited cell proliferation, migration and invasion, but promoted cell apoptosis in SGC-7901 and MKN45 cells. Propofol also elevated the expression of miR-140-5p. Suppression of miR-140-5p could reverse the effects of propofol on the biological behavior of SGC-7901 and MKN45 cells. Meanwhile, propofol treatment increased the expression of cleaved caspase-3 but decreased Bcl-2, MMP-2 and MMP-9 in SGC-7901 and MKN45 cells. The expression of cleaved caspase-3 was downregulated while Bcl-2, MMP-2 and MMP-9 were upregulated by miR-140-5p suppression.ConclusionPropofol could inhibit cell proliferation, migration and invasion, as well as promote cell apoptosis by upregulating miR-140-5p in gastric cancer cells.

The Effects of Propofol on the Human Blood Brain Barrier

Background and Hypothesis: Recently, the safety of repeated and lengthy anesthesia in young children has been called into question. Previous studies have shown propofol, an anesthetic, can diminish blood-brain barrier (BBB) properties. However, the underlying cellular mechanisms are relatively unknown. The BBB is critical in ensuring that potentially harmful circulating factors are impermeable to the brain. Previous animal studies models have shown that propofol increases the levels of matrix metalloproteinases (MMPs), which have independently been shown to degrade the extracellular matrix and breakdown tight junctions, a critical component of the BBB. Hypothesis: Propofol exposure to a human induced pluripotent stem cell (iPSC)-derived BBB model increases MMP activity ultimately contributing to a leaky barrier phenotype.&#x0D; Experimental Design or Project Methods: This study utilized human iPSCs differentiated into brain microvascular endothelial cells (BMECs), the barrier forming cell type of the BBB. iPSC-derived BMECS were exposed to propofol (50μM) for three hours and barrier properties were monitored. Barrier tightness was monitored using trans-endothelial electrical resistance (TEER) and sodium fluorescein permeability assays. Tight junction localization was determined with immunocytochemistry. MMP activity was determined with SensoLyte assay kits. To determine the role of MMPs, a broad spectrum MMP inhibitor, GM6001, was utilized and barrier properties were monitored.&#x0D; Results: Propofol treatment significantly reduced TEER and increased sodium fluorescein permeability, indicative of a leaky barrier. Propofol treatment increased levels of MMP-2 activity but not MMP-9 when compared to non-treated BMECs. Inhibition of MMPs by GM6001 prior to propofol treatment appeared to partially restore barrier integrity as monitored by sodium fluorescein permeability.&#x0D; Conclusion and Potential Impact: These results indicate that increased MMP-2 activity levels could be in part responsible for diminished BBB properties. Inhibition of MMPs protected barrier integrity from propofol treatment. A further understanding of the underlying mechanisms of anesthetic-induced damage can potentially improve anesthesia safety.&#x0D;

GAS5, a FoxO1-actived long noncoding RNA, promotes propofol-induced oral squamous cell carcinoma apoptosis by regulating the miR-1297-GSK3β axis

Propofol, an intravenous anaesthetic agent, has been found to exhibit antitumour effects in various kinds of cancer cells. However, the potential roles and regulatory mechanisms of propofol in oral squamous cell carcinoma (OSCC) remain unknown. Herein, we found that propofol inhibits OSCC cell growth and promotes cell apoptosis in a dose- and time-dependent manner. Further mechanistic studies revealed that the long noncoding RNA GAS5 is induced by propofol in OSCC cells. Elevated GAS5 acts as a competing endogenous RNA for miR-1297 and attenuates its inhibitory effect on GSK3β, leading to GSK3β increase and Mcl1 decrease. Additionally, we found that FoxO1 binds to the promoter of GAS5, facilitating its transcription in response to propofol treatment. Thus, these results suggest that propofol exhibits antitumour effects in OSCC cells and that the FoxO1-GAS5-miR-1297-GSK3β axis plays an important role in propofol-induced OSCC cell apoptosis.